Diseases related to oxidative ageing are becoming increasingly evident in younger individuals. In this study, we investigated the mechanisms underlying the actions of mogroside V when used to treat anti-oxidative ageing.

We used D-galactose-induced LO2 cells and C57BL/6J mice as models to investigate the molecular mechanisms of mogroside V (MV) for the treatment of oxidative ageing. Network pharmacology was used to predict the targets of MV for the treatment of oxidative ageing.

By down-regulating the EGFR/p38/JNK pathway, MV significantly inhibited oxidative ageing and apoptosis in cells, reduced the levels of SA-β-galactosidase. In mice, compared with the model group, MV treatment (100 mg/kg·d) reduced MDA levels and significantly increased the levels of GSH and SOD; furthermore, the size and structure of the liver leaflet and glomeruli was arranged in a regular manner; the small intestine glands had decreased in size. Moreover, the expression levels of Ptp1b mRNA had increased significantly while the levels of c-Jun mRNA and protein were significantly reduced. MV also increased the proportion of beneficial bacteria in the small intestine, including Bacteroidales and Lactobacillaceae.

Our analyses revealed that MV can significantly reduce oxidative ageing caused by the accumulation of D-galactose.

The gut-brain axis (GBA) denotes the dynamic and bidirectional communication system that connects the gastrointestinal tract and the central nervous system (CNS). This review explored this axis, focusing on the role of microbial diversity and fitness in maintaining gastrointestinal health and preventing neurodegeneration, particularly in Alzheimer's disease (AD). Gut dysbiosis, characterized by the imbalance in populations of beneficial and harmful bacteria, has been associated with increased systemic inflammation, neuroinflammation, and the progression of AD through pathogenic mechanisms involving amyloid deposition, tauopathy, and increased blood-brain barrier (BBB) permeability. Emerging evidence highlighted the therapeutic potential of probiotics, dietary interventions, and intermittent fasting in restoring microbial balance, reducing inflammation, and minimizing neurodegenerative risks. Probiotics and synbiotics are promising in helping improve cognitive function and metabolic health, while dietary patterns like the Mediterranean diet were linked to decreased neuroinflammation and enhanced gut-brain communication. Despite significant advancement, further research is needed to elucidate the specific microbial strains, metabolites, and mechanisms influencing brain health. Future studies employing longitudinal designs and advanced omics technologies are essential to developing targeted microbiome-based therapies for managing AD-related disorders.

This study aimed to isolate and characterize an acetylcholine-producing probiotic strain and to evaluate its potential anti-Alzheimer properties in D-galactose rat model. Nine Lactobacillus isolates were isolated and purified on MRS agar, with six demonstrating acetylcholine (ACh) production capability. Among these, Lactiplantibacillus sp. AM2 showed the highest ACh production (78.4 pg/mL) and was identified as Lactiplantibacillus plantarum through morphological, biochemical, 16S rRNA sequencing and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). The in-vitro probiotic characterization of Lactiplantibacillus plantarum AM2 included tolerance testing for acidic conditions and bile salts, viability under simulated digestive conditions, antimicrobial activity assessment, and sensitivity testing to antibiotics. Behavioral and biochemical tests were conducted in a D-galactose-induced cognitive impairment rat model to evaluate cognitive performance, serum glucose levels, oxidative stress markers, and antioxidant capacity. Histopathological evaluations of the hippocampus were also performed. Lactiplantibacillus plantarum AM2 demonstrated strong tolerance to acidic conditions and bile salts, maintaining over 80% viability after exposure to simulated gastric and pancreatic juices. The strain showed hydrophobicity toward hexadecane, octane, and xylene. It also exhibited significant antimicrobial activity against pathogenic bacteria and was sensitive to multiple antibiotics. In cognitive impairment tests, rats administered with Lactiplantibacillus plantarum AM2 showed reduced time latency in the Morris Water Maze, suggesting cognitive enhancement. Biochemical analyses revealed improvements in serum glucose levels, reduced oxidative stress markers, and increased glutathione and total antioxidant capacity. Histopathological analyses showed mitigation of hippocampal damage, promoting recovery of normal cellular architecture. These findings highlight Lactiplantibacillus plantarum AM2 as a promising probiotic candidate with neuroprotective potential and notable ACh production. Further research is warranted to explore its application in therapeutic contexts.

Indian traditional medicine has long utilized medicinal plants for the management of chronic diseases such as Diabetes mellitus (DM) and related neurological complications, Alzheimer's disease (AD). The growing global burden of DM and its associated complications continues to rise; hence, it seems essential to explore effective, targeted therapies to mitigate their progression. Plant-based therapeutics have garnered significant attention for their safety, efficacy and ability to modulate multiple biological pathways. Indigenous medicinal plants, such as Sesbania grandiflora (L.) Poir., Moringa oleifera Lam., Centella asiatica (L.) Urb., Psidium guajava (L.), Aegle marmelos (L.) Corrêa, and Catharanthus roseus (L.) G. Don has been historically employed in ethnomedicine such as classical Ayurvedic texts, scientific literature and has a comprehensive and synergistic approach to address symptoms associated with DM and cognitive decline.

This review explores the interwined pathophysiological pathways between DM and AD, highlighting the potential of medicinal plants through (pre-clinical and clinical evidence), bridging the therapeutic gap. Additionally, we also discussed the currently used conventional antidiabetic drug that has been employed for managing AD.

In this study, six ayurvedic plants with dual activity against DM and AD are thoroughly reviewed with historical context, preclinical and clinical context. The plant's secondary metabolites have demonstrated significant antidiabetic and neuroprotective activities by regulating glucose metabolism, reducing oxidative stress, preventing amyloid-beta accumulation, etc. CONCLUSION: DM and AD share pathophysiology and multifaceted causes, requiring multi-targeted herbal remedies. The selected six Ayurveda medicinal plants showcase the dual benefits for both diseases. The obstacles, such as stability, pharmacokinetics, and safety, remain substantial barriers; addressing these challenges could constrain the clinical translation. This review demands further research to address the challenges to facilitate the effective integration of traditional medicinal knowledge with contemporary practice.

Depression is a common mental condition with high prevalence and recurrence rates worldwide. The active polyphenols in Rosmarinus officinalis L. contain several pharmacological activities, including anti-inflammatory, antibacterial, and neuroprotective characteristics. However, the effects of rosemary polyphenols on depression have not been thoroughly studied. The anti-inflammatory activity and regulatory effects on gut microbiota of key rosemary polyphenols, as well as their impacts on depression, are the main emphasis of this research. We conclude that the anti-depressive effects of rosemary polyphenols are due to anti-inflammatory properties and bidirectional relationship with gut microbiota, including inhibiting inflammatory pathways and cytokines (reducing pro-inflammation cytokines, suppressing NF-κB and NLRP3 inflammasomes, and upregulating Nrf2/HO-1 pathway), altering intestinal microbiota structure and metabolites (polyphenols-related microbial metabolites and biotransformation of polyphenols by microbiota). This paper provides a better understanding of the anti-depressive effects of polyphenols in Rosmarinus officinalis L.

Medicinal plants and their phytochemicals have been extensively employed worldwide for centuries to address a diverse range of ailments, boasting a history that spans several decades. These plants are considered the source of numerous medicinal compounds. For instance, silymarin is a polyphenolic flavonoid extract obtained from the milk thistle plant or Silybum marianum which has been shown to have significant neuroprotective effects and great therapeutic benefits. Neurodegenerative diseases (NDs) are a class of neurological diseases that have become more prevalent in recent years, and although treatment is available, there is no complete cure developed yet. Silymarin utilizes a range of molecular mechanisms, including modulation of MAPK, AMPK, NF-κB, mTOR, and PI3K/Akt pathways, along with various receptors, enzymes, and growth factors. These mechanisms collectively contribute to its protective effects against NDs such as Alzheimer's disease, Parkinson's disease, and depression. Despite its safety and efficacy, silymarin faces challenges related to bioavailability and aqueous solubility, hindering its development as a clinical drug. This review highlights the molecular mechanisms underlying silymarin's neuroprotective effects, suggesting its potential as a promising therapeutic strategy for NDs.

Brain functional changes and gut microbiota dysbiosis have been observed in perimenopausal syndrome (PMS). We evaluated the effects of a plant-based daily diet enriched with Raphanus sativus L. (RSL, radish seed) on the gut microbiota composition, gastrointestinal symptoms, resting-state local spontaneous brain activity, and neuropsychology in perimenopausal women. For 12 weeks, the participants were instructed to adhere to a controlled, Raphanus sativus L.-rich plant-based diet (a mean RSL intake of 5 g/day). Two test days were organized: before and after the nutritional intervention. The fecal microbiota composition, gastrointestinal symptoms, resting-state brain function, and neuropsychology were assessed twice. A longitudinal single-arm study was conducted on 24 perimenopausal women. The Montreal Cognitive Assessment (MoCA) scores tended to improve in the visuospatial/executive function subitem and in the total score after the diet. The participants presented elevated amplitude of low-frequency fluctuation (ALFF) values in the left middle occipital gyrus, the left precentral gyrus, and the left middle cingulum gyrus. The abundances of the phyla Synergistetes and Verrucomicrobia were positively correlated with the ALFF values of the left middle occipital gyrus, left precentral gyrus, and left middle cingulum gyrus. These data suggest that specific gut microbes may modulate intrinsic brain activity and cognitive function in perimenopausal women. A plant-based RSL-rich diet has beneficial effects on the gut microbial composition and brain function of perimenopausal women.

While existing meta-analysis suggest that probiotic therapies may enhance cognitive functions and influence metabolic characteristics, the findings have been inconclusive. In light of these discrepancies, our study undertakes an umbrella review to more precisely determine the aggregate effects and rigorously evaluate the credibility and quality of evidence.

We conducted a systematic search across seven databases, including PubMed, Embase, the Cochrane Library, ProQuest, Web of Science, CINAHL, and Scopus, from their inception to June 20, 2024. We utilized the AMSTAR-2 tool to evaluate the quality of the meta-analyses and applied the GRADE system to rate the quality of the evidence. We estimated the final effect sizes (ESs) along with their 95% confidence intervals (CI) and performed both sensitivity and subgroup analyses to explore the sources of heterogeneity.

Among the 314 articles identified in our search, 13 meta-analysis that met the criteria were included in the study. The quality of the evidence in these studies was graded from high to very low. Our results demonstrate that probiotic treatment significantly enhances cognitive function in patients (ESSMD = 0.39, 95%CI: 0.19 to 0.59, p < 0.001). Moreover, probiotic treatment notably decreased level of serum malondialdehyde (MDA), insulin resistance as detected by homeostasis model assessment method (HOMA-IR) and high-sensitivity C-reactive protein (hs-CRP) (p < 0.001). Conversely, probiotic treatment did not significantly impact triglycerides and very-low-density lipoprotein (VLDL) in patients (p > 0.05).

Although preliminary evidence indicated that probiotic therapy may positively impact cognitive function, MDA, HOMA-IR, and hs-CRP, the overall quality of the existing evidence is insufficient to provide strong support. Therefore, future research must employ more rigorous designs or initiate larger clinical trials to produce more compelling evidence to further validate the efficacy of probiotic therapy on cognitive function of patients with cognitive dysfunction.

This study examined the relationship between adherence to the Mediterranean diet, MIND diet, Recommended Food Score (RFS), Alternative Healthy Eating Index (AHEI), and Energy-adjusted Dietary Inflammatory Index (EDII) and dementia risk in a large UK population cohort.

We analyzed data from 131,209 participants in the UK Biobank, aged 40-69 years, with no prior diagnosis of dementia at baseline. Dietary intake was assessed using the validated Oxford WebQ tool, and adherence to each dietary pattern was calculated. Dementia incidence was identified using algorithmically defined outcomes based on ICD codes. Fine-Gray subdistribution hazard models adjusted for sociodemographic, genetic, and lifestyle factors were applied to examine the association between dietary indices and dementia risk. Subgroup analyses were conducted based on age, sex, obesity status, and ApoEε4 status.

Over a median follow-up of 13.5 years, 1453 dementia cases were identified. Higher adherence to the MEDAS, MIND diet, RFS, and AHEI was significantly associated with reduced dementia risk (HRs: 0.79, 0.73, 0.72, and 0.77, respectively). Conversely, higher EDII scores, indicating pro-inflammatory diets, were linked to an increased dementia risk (HR: 1.3). These associations were more pronounced in older adults (≥60 years), women, non-obese individuals, and ApoEε4 non-carriers. Subgroup analyses revealed differential impacts of dietary patterns based on demographic and health-related factors.

Greater adherence to Mediterranean, MIND, and high-quality diets is associated with a lower risk of dementia, while pro-inflammatory diets increase the risk. High-quality anti-inflammatory diets play a significant role in reducing the risk of dementia, with stronger effects observed in specific subgroups.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests. Studies have revealed that gut microbiota and their metabolism play important roles in ASD, and become the underlying mechanisms of ASD.

In this study, we performed long-read 16S rRNA sequencing and untargeted metabolomics to comprehensively characterize the profiles of gut microbiota and fecal metabolites in 34 ASD patients and 18 healthy controls. The associations between gut microbiota, fecal metabolites and clinical symptoms were analyzed to screen related biomarkers for ASD.

The results showed the similarity of the overall microbial richness and diversity between ASD patients and controls, however, some specific bacterial taxa exhibited significant differences, including Klebsiella and Escherichia-Shigella at genera level, and Clostridium-sporogenes, Escherichia-coli-O157H7 and Bacteroides-ovatus at species level. The fecal metabolomics validated that a lot of metabolites had significantly differential levels, including a series of organic acids, amino acids and dopamine.

The associations of gut microbiota and fecal metabolites might shed new light on the pathogenesis of ASD and help us to understand the importance of gut microbiota as potential biomarkers and therapeutic targets in the development of ASD.

Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut-brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut-brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.

Emerging evidence indicates that inflammatory bowel disease (IBD) and dementia may share underlying pathological mechanisms and risk factors. However, the association between a prior IBD diagnosis and the subsequent risk of dementia remains largely unexplored. We conducted a comprehensive search of PubMed, Embase, and the Cochrane Library up to February 4, 2025, without language restrictions. Two reviewers independently extracted data and evaluated methodological quality and risk of bias. Observational studies comparing dementia risk in IBD and non-IBD populations were included. Pooled effect estimates for odds ratios (OR) were calculated using random-effects models. A total of 10 population-based studies, involving 7,895,339 participants (269,387 with IBD), were included. Meta-analysis of eight studies showed a significant association between IBD and dementia risk (OR 1.17, 95% CI: 1.08-1.27, P = 0.0001). However, IBD was not associated with an increased risk of Alzheimer's disease (AD) (OR 1.15, 95% CI: 0.98-1.36, P = 0.09). Stratified analysis by IBD type revealed a positive association between both ulcerative colitis (UC) and Crohn's disease (CD) and dementia risk (UC: OR 1.15, 95% CI: 1.05-1.25, P = 0.002, I² = 81%; CD: OR 1.26, 95% CI: 1.11-1.43, P = 0.0003, I² = 53%). This study identifies a significant correlation between IBD and dementia, suggesting that IBD patients have an elevated risk of developing dementia. However, current evidence is insufficient to establish a causal relationship. Further research should explore whether effective IBD treatments can mitigate this risk and elucidate the underlying pathophysiological mechanisms connecting these conditions.

This study aimed to investigate the relationship between blood microbiota, specifically bacterial DNA, and cognitive decline in individuals with subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI). The objective was to identify potential microbial signatures that could serve as biomarkers for cognitive deterioration.

Forty-seven participants were recruited, including 13 with aMCI, 20 with SCD, and 14 normal cognition (NC). Blood samples were collected, and microbial DNA was analyzed using 16S rRNA sequencing on the Illumina MiSeq platform. Bioinformatics analyses-including α- and β-diversity measures and differential abundance testing (using edgeR)-were employed to assess microbial diversity and differences in bacterial composition among groups. Logistic regression models were used to evaluate the predictive impact of the microbiota on cognitive decline.

Microbial diversity differed significantly between groups, with NC exhibiting the highest α-diversity. Both the aMCI and SCD groups showed reduced diversity. Taxa such as Bacteroidia, Alphaproteobacteria, and Clostridia were significantly decreased in the aMCI group compared to NC (p< 0.05). In contrast, Gammaproteobacteria increased significantly in the aMCI group compared to both NC and SCD, indicating progressive microbial changes from SCD to aMCI. No significant differences were found between the NC and SCD groups.

Distinct bacterial taxa-particularly the increase in Gammaproteobacteria along with decreases in Bacteroidia, Alphaproteobacteria, and Clostridia-are associated with the progression of cognitive decline. These findings suggest that blood microbiota could serve as potential biomarkers for the early detection of aMCI. However, the small sample size and the lack of control for confounding factors such as diet and medication limit the findings. Larger studies are needed to validate these results and further explore the role of microbiota in neurodegeneration.

Gastrodia elata BI., which is an edible plant, has been reported in previous studies to possess a strong capacity for alleviating the symptoms of Alzheimer's disease (AD). This study focuses on ginger-processed and fermented Gastrodia elata BI. (FGGE) to investigate its effects on behaviour, brain neuroregulation, and the gut microbiota in an AlCl3-induced AD rat model, and to explore the underlying mechanisms. Results indicate that FGGE significantly improved novel object recognition and the correct alternation rate in the Y-maze test for AD rats. In addition, FGGE alleviated brain oxidative stress and restored the anti-inflammatory response, cholinergic function, and tissue morphology in the hippocampus. Furthermore, FGGE activated the cAMP response element-binding protein/brain-derived neurotrophic factor signalling pathway, reversing neural network abnormalities and enhancing neural regulation. FGGE also promoted the proliferation of bacteria negatively associated with AD, such as Methanosphaera and Lactobacillus, thereby restoring gut microbiota balance. The mechanisms by which FGGE alleviates AD may involve the modulation of the gut-brain axis, ultimately mitigating AD symptoms. FGGE represents an innovative functional food with significant therapeutic potential and promising application prospects.

The hippocampus executes the integration of memory and spatial learning information. This study evaluated the effect of rice bran extract (RBE) on heavy metal mixture (MM) induced hippocampal toxicity and its underlying mechanism in albino rats. Thirty five rats were exposed to MM alone at Pb 20 mg/kg, Al 35 mg/kg, and Mn 0.564 mg/kg body weight or co-exposed with RBE at 125, 250 and 500 mg/kg body weight, 125 RBE mg/kg b.wt only, and 500 RBE mg/kg b.wt only 5 days a wk for 13 wk (90 days). Subsequently, oxidative stress, inflammation (cyclooxygenase-2) and caspase-3, amyloid precursor proteins (Aβ40 and Aβ42), HMOX-1, occludin and BDNF and transcription factor Nrf-2 in the hippocampus were investigated. MM treatment resulted in significantly higher escape latency time than both the control and MM plus RBE group. MM exposure induced increased oxidative stress, inflammation resulting in enhanced hippocampal apoptosis. MM significantly increased bioaccumulation of Pb, Al, and Pb; increased caspase-3, Nrf-2, Aβ40 and Aβ42 and significantly decreased occludin, BDNF, HMOX-1 when compared with the control. All these effects were reversed by RBE. Collectively, RBE ameliorated MM - induced oxidative stress, neuro-inflammation and hippocampal apoptosis via attenuation of oxidative damages of cellular constituents, neuronal inflammation and subsequent down regulation of amyloid precursor proteins Aβ40, Aβ42 and up regulation of occludin, BDNF, HMOX-1 protein expression via Nrf-2 dependent pathways to abrogate hippocampal toxicity associated with spatial learning and memory deficits.

To better understand the variations in gut microbiota in children with different types of epilepsy.

Thirty-seven children with epilepsy were included in the case group, which was further divided into focal (group A, n = 28) and generalized epilepsy groups (group B, n = 9) based on the origin and extent of the seizures. The focal epilepsy group was subdivided into the benign childhood epilepsy with centrotemporal spikes (BECT) (group C, n = 9) and non-BECT groups (group D, n = 19) based on the appearance of typical centrotemporal spikes or spike-wave complexes on the electroencephalogram (EEG). Additionally, 14 healthy children were selected as the control group (group E, n = 14).

Significant differences were observed in the diversity and composition of gut microbiota between the case and control groups. At the genus level, the abundance of Megamonas (P = 0.001), Streptococcus (P<0.001), Romboutsia (P = 0.001), Bacteroides (P<0.05), and Escherichia/Shigella (P<0.05) was significantly higher in the focal epilepsy group than in the control group (0.027 vs. 0.00009, P = 0.001; 0.016 vs. 0.002, P<0.001; 0.013 vs. 0.002, P = 0.001; 0.030 vs. 0.002, P<0.05, respectively). Additionally, Escherichia/Shigella (P<0.05) was more abundant in the case group compared to the control group (0.033 vs. 0.002, P<0.05). Bacteroides (P<0.05) was more abundant in the control group than in the case group. Megamonas (P<0.001) and Collinsella (P<0.05) were significantly more prevalent in the BECT group than in the control group (0.034 vs. 0.00009, P<0.001; 0.014 vs. 0.001, P<0.05, respectively). In the non-BECT group, compared to the control group, Megamonas (P = 0.013), Streptococcus (P<0.001), Romboutsia (P = 0.001), and Escherichia/Shigella (P<0.05) were found in greater abundance (0.023 vs. 0.00009, P = 0.013; 0.018 vs. 0.002, P<0.001; 0.014 vs. 0.002, P = 0.001; 0.037 vs. 0.002, P<0.05, respectively).

Though, there were no statistically significant differences in gut microbiota between the different types of epilepsy, the gut microbiota of children with epilepsy significantly differed from that of healthy controls. The increased abundance of Escherichia/Shigella may lead to the worsening of clinical phenotypes and poor prognosis, and it could be a candidate biomarker to identify the focal epilepsy or even non-benign childhood epilepsy with centrotemporal spikes, potentially providing new therapeutic targets for the future.

The delivery of biomolecules to target cells has been a longstanding challenge in biotechnology. DNA viruses naturally evolved the ability to deliver genetic material to cells and modulate cellular processes. As such, they inherently possess requisite characteristics that have led to their extensive study, engineering, and development as biotechnological tools. Here, we overview the application of DNA viruses to biotechnology, with specific implications in basic research, health, biomanufacturing, and agriculture. For each application, we review how an increasing understanding of virology and technological methods to genetically manipulate DNA viruses has enabled advances in these fields. Additionally, we highlight the remaining challenges to unlocking the full biotechnological potential of DNA viral technologies. Finally, we discuss the importance of balancing continued technological progress with ethical and biosafety considerations.

Dual-functional peptides exhibiting both anti-amyloid and antimicrobial activities have attracted attention as promising candidates for Alzheimer's disease treatment. The advantage of these peptides lies in their ability to simultaneously target both the amyloid cascade hypothesis and the microbial infection hypothesis, in contrast to single-function inhibitors. However, most of the reported dual-functional peptides to date are natural peptides, and the development of synthetic peptides in this area remains limited. In this study, we propose two strategies to aid in the discovery of synthetic dual-functional peptides. We then report four distinct synthetic dual-functional peptides identified using these strategies, with the Aβ1-40/Aβ1-42 fibrillation system and common bacterial strains serving as a proof-of-concept platform. One strategy involves repurposing existing knowledge, while the other breaks from established conventions. Using the first strategy, we discovered a very short dual-functional linear peptide. With the second strategy, we identified a simple dual-functional cyclic peptide. Furthermore, by combining these two strategies, we developed a hybrid dual-functional peptide incorporating both linear and cyclic structures. We hope that our findings will contribute to the future discovery of more synthetic dual-functional peptides for treating Alzheimer's disease.

The gut microbiota emerged as a potential modulator of brain connectivity in health and disease. This systematic review details current evidence on the gut-brain axis and its influence on brain connectivity. The initial set of studies included 532 papers, updated to January 2024. Studies were selected based on employed techniques. We excluded reviews, studies without connectivity focus, studies on non-human subjects. Forty-nine papers were selected. Employed techniques in healthy subjects included 15 functional magnetic resonance imaging studies (fMRI), 5 diffusion tensor imaging, (DTI) 1 electroencephalography (EEG), 6 structural magnetic resonance imaging, 2 magnetoencephalography, 1 spectroscopy, 2 arterial spin labeling (ASL); in patients 17 fMRI, 6 DTI, 2 EEG, 9 structural MRI, 1 transcranial magnetic stimulation, 1 spectroscopy, 2 R2*MRI. In healthy subjects, the gut microbiota was associated with connectivity of areas implied in cognition, memory, attention and emotions. Among the tested areas, amygdala and temporal cortex showed functional and structural differences based on bacteria abundance, as well as frontal and somatosensory cortices, especially in patients with inflammatory bowel syndrome. Several studies confirmed the connection between microbiota and brain functions in healthy subjects and patients affected by gastrointestinal to renal and psychiatric diseases.

Aging is an extremely significant risk associated with neurodegeneration. The most prevalent neurodegenerative disorders (NDs), such as Alzheimer's disease (AD) are distinguished by the prevalence of proteinopathy, aberrant glial cell activation, oxidative stress, neuroinflammation, defective autophagy, cellular senescence, mitochondrial dysfunction, epigenetic changes, neurogenesis suppression, increased blood-brain barrier permeability, and intestinal dysbiosis that is excessive for the patient's age. Substantial body studies have documented a close relationship between gut microbiota and AD, and restoring a healthy gut microbiota may reduce or even ameliorate AD symptoms and progression. Thus, control of the microbiota in the gut has become an innovative model for clinical management of AD, and rising emphasis is focused on finding new techniques for preventing and/or managing the disease. The etiopathogenesis of gut microbiota in driving AD progression and supplementing postbiotics as a preventive and therapeutic treatment for AD is discussed. The review additionally discusses the use of postbiotics in AD prophylaxis and therapy, portraying them as substances that address senescence-triggered dysfunctions and are worthy of translating from bench to biopharmaceutical market in response to "silver consumers" needs. The current review examines and evaluates the impact of postbiotics as whole and specific metabolites, such as short-chain fatty acids (SCFAs), lactate, polyamines, polyphenols, tryptophan metabolites, exopolysaccharides, and bacterial extracellular vesicles, on the aging-associated processes that reinforce AD. Moreover, it provides an overview of the most recent data from both clinical and preclinical research involving the use of postbiotics in AD.

The gut microbiota, the complex community of microorganisms that inhabit the gastrointestinal tract, has emerged as a key player in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD). AD is characterized by progressive cognitive decline and neuronal loss, associated with the accumulation of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation in the brain. Increasing evidence suggests that alterations in the composition and function of the gut microbiota, known as dysbiosis, may contribute to the development and progression of AD by modulating neuroinflammation, a chronic and maladaptive immune response in the central nervous system. This review aims to comprehensively analyze the current role of the gut microbiota in regulating neuroinflammation and glial cell function in AD. Its objective is to deepen our understanding of the pathogenesis of AD and to discuss the potential advantages and challenges of using gut microbiota modulation as a novel approach for the diagnosis, treatment, and prevention of AD.

The effect of digestion on nanocarriers will affect the release and pharmacological effects of bioactive compounds in delivery systems. The digestion of cellulose is limited to gut microbiota, which offers a new research strategy for targeted delivery of bioactive compounds. Herein, positively charged cellulose-like chitosan/polyvinylpyrrolidone nanofiber was prepared to improve the residence time, colon target and gut microbiota regulation activity of quercetin decorated selenium nanoparticles (QUE@SeNPs/CS/PVPNFs). Selenium nanoparticles block the degradation of quercetin and QUE@SeNPs/CS/PVPNFs only decompose when caused by chitosanase secretion from gut microbiota. In vivo imaging showed that the residence time of QUE@SeNPs/CS/PVPNFs was longer than that of QUE@SeNPs. Thus, it significantly decreased the lipid concentrations in liver, which further inhibited insulin resistance in mice. Moreover, QUE@SeNPs/CS/PVPNFs treatment improves gut barrier integrity, increased the relative abundance of anti-obesity and anti-inflammation related bacterial including Akkermansia, Lactobacillus and Bacteroides. Consequently, the inflammatory factor (IL-β and TNF-α) levels in gut, liver and brain were also decreased. Nissl and PSD-95 staining indicated that QUE@SeNPs/CS/PVPNFs ameliorated synapse dysfunction in the brain. Therefore, QUE@SeNPs/CS/PVPNFs has a greater effect than QUE@SeNPs in improving cognitive ability in Morris water maze. Overall, QUE@SeNPs/CS/PVPNFs with prolonged residence time attenuates cognitive disorder via gut-liver-brain axis in AD.

Background: The gut microbiome directly impacts brain health and activity, meaning the two are closely associated. This relationship suggests a link between microbial imbalances and diseases such as Alzheimer's, although multiple other contributing factors, such as genetics, also play a part. Additionally, recent studies discovered that cerebrospinal fluid has some microbial deoxyribonucleic acid (DNA), which can be interpreted to mean a microbiome exists in the brain too. The vagus nerve and the central nervous and immune systems are responsible for the connection between the brain and gut microbiome. Aims and Objectives: The main aim of this systematic review is to analyze existing research on the gut-brain axis and the brain microbiome to fill the current knowledge gap. Materials and Methods: A search was conducted on the PubMed database based on a set of predefined MeSH terms. Results: After the search, 2716 articles meeting the MeSH parameters were found in PubMed. This list was then downloaded and analyzed according to the inclusion/exclusion criteria, and 63 relevant papers were selected. Discussion: Bacteria in the gut microbiome produce some substances that are considered neuroactive. These compounds can directly or indirectly affect brain function through the gut-brain axis. However, various knowledge gaps on the mechanisms involved in this connection need to be addressed first.

Gut microbiota dysbiosis is linked to Alzheimer's disease (AD), but our understanding of the molecular and neuropathological bases underlying such association remains fragmentary.

Using 16S rDNA amplicon sequencing, untargeted metabolomics, and multi-modal magnetic resonance imaging, we examined group differences in gut microbiome, fecal metabolome, neuroimaging measures, and cognitive variables across 30 patients with AD, 75 individuals with mild cognitive impairment (MCI), and 61 healthy controls (HC). Furthermore, we assessed the associations between these multi-omics changes using correlation and mediation analyses.

There were significant group differences in gut microbial composition, which were driven by 8 microbial taxa (e.g., Staphylococcus and Bacillus) exhibiting a progressive increase in relative abundance from HC to MCI to AD, and 2 taxa (e.g., Anaerostipes) showing a gradual decrease. 26 fecal metabolites (e.g., Arachidonic, Adrenic, and Lithocholic acids) exhibited a progressive increase from HC to MCI to AD. We also observed progressive gray matter atrophy in broadly distributed gray matter regions and gradual micro-structural integrity damage in widespread white matter tracts along the AD continuum. Integration of these multi-omics changes revealed significant associations between microbiota, metabolites, neuroimaging, and cognition. More importantly, we identified two potential mediation pathways: (1) microbiota → metabolites → neuroimaging → cognition, and (2) microbiota → metabolites → cognition.

Aside from elucidating the underlying mechanism whereby gut microbiota dysbiosis is linked to AD, our findings may contribute to groundwork for future interventions targeting the microbiota-metabolites-brain-cognition pathways as a therapeutic strategy in the AD continuum.

Over the past several decades, high-resolution brain imaging, blood and cerebrospinal fluid analyses, and other advanced technologies have changed diagnosis from an exercise depending primarily on the history and physical examination to a computer- and online resource-aided process that relies on larger and larger quantities of data. In addition, randomized controlled trials (RCT) at a population level have led to many new drugs and devices to treat neurological disease, including disease-modifying therapies. We are now at a crossroads. Combinatorially profound increases in data about individuals has led to an alternative to population-based RCTs. Genotyping and comprehensive "deep" phenotyping can sort individuals into smaller groups, enabling precise medical decisions at a personal level. In neurology, precision medicine that includes prediction, prevention and personalization requires that genomic and phenomic information further incorporate imaging and behavioral data. In this article, we review the genomic, phenomic, and computational aspects of precision medicine for neurology. After defining biological markers, we discuss some applications of these "-omic" and neuroimaging measures, and then outline the role of computation and ultimately brain simulation. We conclude the article with a discussion of the relation between precision medicine and value-based care.

The complex pathophysiology of Alzheimer's disease (AD) poses challenges for the development of therapies. Recently, neuroinflammation has been identified as a key pathogenic mechanism underlying AD, while inflammation has emerged as a possible target for the management and prevention of AD. Several prior studies have demonstrated that medications modulating neuroinflammation might lessen AD symptoms, mostly by controlling neuroinflammatory signaling pathways such as the NF-κB, MAPK, NLRP3, etc, and their respective signaling cascade. Moreover, targeting these inflammatory modalities with inhibitors, natural products, and metabolites has been the subject of intensive research because of their anti-inflammatory characteristics, with many studies demonstrating noteworthy pharmacological capabilities and potential clinical applications. Therefore, targeting inflammation is considered a promising strategy for treating AD. This review comprehensively elucidates the neuroinflammatory mechanisms underlying AD progression and the beneficial effects of inhibitors, natural products, and metabolites in AD treatment.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and progressive neuronal damage. Recent research has highlighted the significant roles of the gut microbiota and microRNAs (miRNAs) in the pathogenesis of AD. This review explores the intricate interaction between gut microbiota and miRNAs, emphasizing their combined impact on Alzheimer's progression. First, we discuss the bidirectional communication within the gut-brain axis and how gut dysbiosis contributes to neuroinflammation and neurodegeneration in AD. Changes in gut microbiota composition in Alzheimer's patients have been linked to inflammation, which exacerbates disease progression. Next, we delve into the biology of miRNAs, focusing on their roles in gene regulation, neurodevelopment, and neurodegeneration. Dysregulated miRNAs are implicated in AD pathogenesis, influencing key processes like inflammation, tau pathology, and amyloid deposition. We then examine how the gut microbiota modulates miRNA expression, particularly in the brain, potentially altering neuroinflammatory responses and synaptic plasticity. The interplay between gut microbiota and miRNAs also affects blood-brain barrier integrity, further contributing to Alzheimer's pathology. Lastly, we explore therapeutic strategies targeting this gut microbiota-miRNA axis, including probiotics, prebiotics, and dietary interventions, aiming to modulate miRNA expression and improve AD outcomes. While promising, challenges remain in fully elucidating these interactions and translating them into effective therapies. This review highlights the importance of understanding the gut microbiota-miRNA relationship in AD, offering potential pathways for novel therapeutic approaches aimed at mitigating the disease's progression.

Alzheimer's disease (AD), a debilitating neurodegenerative disorder, remains one of the foremost public health challenges affecting more than 30 million people worldwide with the etiology still largely enigmatic. The intricate gut-brain axis, serving as a vital communication network between the gut and the brain, appears to wield influence in the progression of AD. Our study showcases the remarkable precision of x-ray phase-contrast tomography (XPCT) in conducting an advanced three-dimensional examination of gut cellular composition and structure. The exploitation of micro- and nano-XPCT on various AD mouse models unveiled relevant alterations in villi and crypts, cellular transformations in Paneth and goblet cells, along with the detection of telocytes, neurons, erythrocytes, and mucus secretion by goblet cells within the gut cavity. The observed gut structural variations may elucidate the transition from dysbiosis to neurodegeneration and cognitive decline. Leveraging XPCT could prove pivotal in early detection and prognosis of the disease.

Low vitamin D status is linked to disturbance in cognitive performance. This study explored possible ways how composition and functional capacity of the gut microbiome affects vitamin D metabolism, directing serum vitamin D (VitD) levels and memory impairmets. It was found that gut microbiome composition, characterized by an increase in the relative abundance of Enterococcus and correlated with vitamin D deficiency and, as consequence, with memory impairments. A key mechanism identified in the study was the differential utilization of short-chain fatty acids (SCFAs) produced by gut bacteria as substrates for synthesizing vitamin D3 precursor in the skin. This finding confirms a complex interplay between the gut microbiome, host metabolism, and cognitive health, highlighting the potential significance of targeting Enterococcus dysbiosis in future preventive and therapeutic strategies to address VitD deficiency-related memory impairments. These results underscore the importance of understanding and modulating gut microbiome composition to optimize VitD status and cognitive function.

The gut microbiome is a complex system that directly interacts with and influences many systems in the body. This delicate balance of microbiota plays an important role in health and disease and is highly influenced by lifestyle factors and the surrounding environment. As further research emerges, understanding the full potential of the gut microbiome and the impact of using nutraceuticals to positively influence its function may open the door to greater therapeutic outcomes in the treatment and prevention of disease. Curcumin, a bioactive compound derived from the turmeric rhizome, has been studied in depth for its influence on human health as a potent anti-inflammatory and antioxidant properties. However, the therapeutic activity of curcumin is limited by its low oral bioavailability. While most available research has primarily focused on the curcuminoid compounds of turmeric, the non-curcuminoid compounds hold promise to offer therapeutic benefits while synergistically enhancing the bioavailability of curcumin and supporting the gut microbiome. This review summarizes current knowledge of the relationship between the gut and the various systems within the body, and how dysbiosis, or disruption in the gut microbial balance, leads to inflammation and increased risk of chronic disease. The review also summarizes recent research that focuses on the bioactivity of both the curcuminoid and non-curcuminoid compounds that comprise the whole turmeric root and their synergistic role in enhancing bioavailability to support a healthy gut microbiome and promising use in the treatment and prevention of disease.

Background/Objectives: This systematic review focused on collecting the most significant findings on the impact of the administration of Bifidobacterium infantis (or Bifidobacterium longum subps. infantis) and Bifidobacterium breve, alone, in conjunction, or in combination with other strains, in the treatment of neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). These diseases are characterized by the progressive degeneration of neurons, resulting in a broad spectrum of clinical manifestations. AD is typified by a progressive decline in cognitive abilities, while PD is marked by motor symptoms associated with the loss of dopamine (DA). Methods: Five different databases, ScienceDirect, Scopus, Wiley, PubMed, and Web of Science (WoS), were reviewed and the studies were screened for inclusion by the following criteria: (i) studies that specifically evaluated the use of Bifidobacterium infantis, Bifidobacterium longum subsp. infantis, or Bifidobacterium breve as a therapeutic intervention, either in human or animal models, in the context of neurodegenerative diseases; (ii) the studies were required to address one or more of the pathologies examined in this article, and the pathologies included, but were not limited to, neurodegeneration, Alzheimer's disease, Parkinson's disease, and oxidative stress; (iii) the full text was accessible online; and (iv) the article was written in English. Results: The data suggest that these probiotics have neuroprotective effects that may delay disease progression. Conclusions: This study provides updated insights into the use of these Bifidobacterium strains in neurodegenerative diseases like AD and PD, with the main limitation being the limited number of clinical trials available.

Alzheimer's disease (AD) is a common central neurodegenerative disease disorder characterized primarily by cognitive impairment and non-cognitive neuropsychiatric symptoms that significantly impact patients' daily lives and behavioral functioning. The pathogenesis of AD remains unclear and current Western medicines treatment are purely symptomatic, with a singular pathway, limited efficacy, and substantial toxicity and side effects. In recent years, as research into AD has deepened, there has been a gradual increase in the exploration and application of medicinal plants for the treatment of AD. Numerous studies have shown that medicinal plants and their active ingredients can potentially mitigate AD by regulating various molecular mechanisms, including the production and aggregation of pathological proteins, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, neurogenesis, neurotransmission, and the brain-gut microbiota axis. In this review, we analyzed the pathogenesis of AD and comprehensively summarized recent advancements in research on medicinal plants for the treatment of AD, along with their underlying mechanisms and clinical evidence. Ultimately, we aimed to provide a reference for further investigation into the specific mechanisms through which medicinal plants prevent and treat AD, as well as for the identification of efficacious active ingredients derived from medicinal plants.

The gut and the gut microbiome communicate with the nervous system through the gut-brain axis via neuroimmune and neuroendocrine mechanisms. Despite existing research, studies exploring this link in aging dogs are limited. This study aims to examine multiple blood and fecal biomarkers of intestinal health, along with various behavioral indicators based on saliva, blood, observations, and activity, in different age populations (junior: <2 y.o.; adult: 2-7 y.o.; senior: >7 y.o.) of thirty-seven Beagle dogs. In our study, Bacteroides were significantly higher in senior dogs. The relative abundance of Faecalibacterium and Blautia showed age-related trends, higher in senior and junior dogs, respectively. Fecal short-chain fatty acid concentration, especially acetate, increased with age, while propionate was higher in junior dogs. For the behavioral indicators we considered, blood thyroxine concentration, playing, exploring, and total activity were higher in junior dogs. The differences observed between the biomarkers of gut health and behavior, particularly those significant for the age correlations, emphasize the importance of considering age-related factors when studying the gut microbiome and behavior. However, further research is needed to better understand the mechanisms and specific pathways involved in the relationship between the studied biomarkers and age.

The primary source of short-chain fatty acids (SCFAs), now recognized as critical mediators of host health, particularly in the context of neurobiology and cancer development, is the gut microbiota's fermentation of dietary fibers. Recent research highlights the complex influence of SCFAs, such as acetate, propionate, and butyrate, on brain cancer progression. These SCFAs impact immune modulation and the tumor microenvironment, particularly in brain tumors like glioma. They play a critical role in regulating cellular processes, including apoptosis, cell differentiation, and inflammation. Moreover, studies have linked SCFAs to maintaining the integrity of the blood-brain barrier (BBB), suggesting a protective role in preventing tumor infiltration and enhancing anti-tumor immunity. As our understanding of the gut-brain axis deepens, it becomes increasingly important to investigate SCFAs' therapeutic potential in brain cancer management. Looking into how SCFAs affect brain tumor cells and the environment around them could lead to new ways to prevent and treat these diseases, which could lead to better outcomes for people who are dealing with these challenging cancers.

The Gut-Brain Axis (GBA) is a crucial link between the gut microbiota and the central nervous system. Xenobiotics, originating from diverse sources, play a significant role in shaping this interaction. This review examines how these compounds influence neurotransmitter dynamics within the GBA. Environmental pollutants can disrupt microbial populations, impacting neurotransmitter synthesis-especially serotonin, gamma-aminobutyric acid (GABA), and dopamine pathways. Such disruptions affect mood regulation, cognition, and overall neurological function. Xenobiotics also contribute to the pathophysiology of neurological disorders, with changes in serotonin levels linked to mood disorders and imbalances in GABA and dopamine associated with anxiety, stress, and reward pathway disorders. These alterations extend beyond the GBA, leading to complications in neurological health, including increased risk of neurodegenerative diseases due to neuroinflammation triggered by neurotransmitter imbalances. This review provides a comprehensive overview of how xenobiotics influence the GBA and their implications for neurological well-being.

Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD. Additionally, disruption of the gut microbiota has been found to be associated with AD, and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach. However, the precise mechanism of FMT in the treatment of AD remains elusive. In this study, FMT was performed by transplanting fecal microbiota from healthy wild-type mice into APP/PS1 mice (APPswe, PSEN1dE9) to assess the effectiveness of FMT in mitigating AD-associated inflammation and to reveal its precise mechanism of action. The results demonstrated that FMT treatment improved cognitive function and reduced the expression levels of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway in mice, which was accompanied by the restoration of gut microbial dysbiosis. These findings suggest that FMT has the potential to ameliorate AD symptoms and delay the disease progression in APP/PS1 mice.

The Receptor for Advanced Glycation End Products (RAGE), part of the immunoglobulin superfamily, plays a significant role in various essential functions under both normal and pathological conditions, especially in the progression of Alzheimer's disease (AD). RAGE engages with several damage-associated molecular patterns (DAMPs), including advanced glycation end products (AGEs), beta-amyloid peptide (Aβ), high mobility group box 1 (HMGB1), and S100 calcium-binding proteins. This interaction impairs the brain's ability to clear Aβ, resulting in increased Aβ accumulation, neuronal injury, and mitochondrial dysfunction. This further promotes inflammatory responses and oxidative stress, ultimately leading to a range of age-related diseases. Given RAGE's significant role in AD, inhibitors that target RAGE and its ligands hold promise as new strategies for treating AD, offering new possibilities for alleviating and treating this serious neurodegenerative disease. This article reviews the various pathogenic mechanisms of AD and summarizes the literature on the interaction between RAGE and its ligands in various AD-related pathological processes, with a particular focus on the evidence and mechanisms by which RAGE interactions with AGEs, HMGB1, Aβ, and S100 proteins induce cognitive impairment in AD. Furthermore, the article discusses the principles of action of RAGE inhibitors and inhibitors targeting RAGE-ligand interactions, along with relevant clinical trials.

Growing evidence suggests that the gut-brain axis influences brain function, particularly the role of intestinal microbiota in modulating cognitive processes. Probiotics may alter brain function and behavior by modulating gut microbiota, with implications for neurodegenerative diseases like Alzheimer's disease (AD). The purpose of this review is to systematically review the current literature exploring the effects of probiotic supplementation on gut microbiota and cognitive function in AD and mild cognitive impairment (MCI).

A comprehensive literature search was conducted across PubMed/Medline, Embase, and Scopus to identify relevant randomized controlled trials (RCTs) from inception to 20 August 2024. The search focused on comparing outcomes between intervention and control/placebo groups. Data searches, article selection, data extraction, and risk of bias assessment were performed in accordance with Cochrane guidelines.

PROSPERO registration no: CRD42023446796.

Data from four RCTs involving 293 Individuals (AD and MCI patients) receiving mainly Lactobacillus and Bifidobacterium strains showed some beneficial effects on cognitive function, altered gut microbiota composition, and positively affected metabolic biomarkers. However, variability in microbiota assessment across studies limits the interpretation of results. The limited number and quality of the existing studies make it difficult to draw definitive conclusions from the data. Additional high-quality research is clearly needed.

Probiotics show promise as an adjunctive intervention for cognitive decline, but larger, long-term trials are needed to confirm their efficacy and clinical applicability in neurodegenerative diseases like AD.

This study addresses the complex multifactorial causes of Alzheimer's disease (AD) and colorectal cancer (CRC), two significant public health issues. Despite previous research, the precise relationship between AD and CRC remains unclear. This study aimed to explore the potential causal relationship between AD and CRC using Mendelian randomization (MR) and to identify risk genes through colocalization and transcriptomic analyses.

The study used a two-sample Mendelian randomization (MR) approach to investigate the causal effect of AD on CRC. Genome-wide association study (GWAS) summary statistics for AD and CRC were utilized. Colocalization analysis was conducted to identify risk genes associated with AD, which were then validated through transcriptomic analysis in CRC samples. The study used GWAS data from a cohort of European patients and applied several MR methods, including MR Egger, weighted median, and inverse-variance weighted approaches, to ensure robust findings.

The MR analysis revealed a significant positive causal relationship between AD and CRC, indicating that an increased genetic predisposition to AD is associated with a elevated risk of developing CRC. The colocalization analysis identified COLEC11 as a significant risk gene for AD, which also showed a strong positive correlation with clinical features and survival outcomes in CRC. Elevated COLEC11 expression was linked to advanced clinical stages, increased tumor mutational burden, microsatellite instability, and poorer overall survival in CRC patients.

This study provides evidence of a causal relationship between AD and CRC, suggesting that shared genetic and inflammatory pathways may underlie both conditions. The identification of COLEC11 as a potential link between AD and CRC offers new avenues for research and therapeutic interventions. These findings contribute to a deeper understanding of the interplay between neurodegenerative and oncologic diseases, highlighting the importance of exploring common pathogenic mechanisms.