• ARIA
• Alzheimer’s disease
• Amyloid-beta
• Blood brain barrier
• Cerebral amyloid angiopathy
• Immunotherapy
• Microglia
• Mouse models
• Neuronal dysfunction

• Animals
• Alzheimer Disease/therapy
• Alzheimer Disease/immunology
• Amyloid beta-Peptides/immunology
• Amyloid beta-Peptides/metabolism
• Immunotherapy/methods
• Disease Models, Animal
• Mice
• Humans
• Mice, Transgenic

• T32AG071745 NIA NIH HHS
• National Institute on Aging

• amyloid β-protein
• amyloidosis
• biological seeds
• cognitive decline
• intracerebral inoculation
• tau pathology

• Alzheimer Disease/metabolism
• Alzheimer Disease/pathology
• Amyloid beta-Peptides/metabolism
• Humans
• Animals
• Disease Models, Animal
• Plaque, Amyloid/metabolism
• Plaque, Amyloid/pathology
• tau Proteins/metabolism

• 32471010 National Natural Science Foundation of China
• 32100800 National Natural Science Foundation of China
• 2023B0303040004 Key-Area Research and Development Program of Guangdong Province
• JCYJ20220818100802005 Shenzhen Science and Technology Program
• KQTD20210811090117032 Shenzhen Science and Technology Program
• ZDSYS20220304163558001 Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases

• Alzheimer’s disease
• Animal models
• Biomarkers
• Neurodegeneration
• Non-human primates
• Parkinson disease
• Spinocerebellar ataxia-1

• Animals
• Disease Models, Animal
• Biomarkers/metabolism
• Humans
• Neurodegenerative Diseases/metabolism
• Neurodegenerative Diseases/pathology
• Neurodegenerative Diseases/diagnosis
• Alzheimer Disease/pathology
• Alzheimer Disease/metabolism
• Alzheimer Disease/diagnosis
• Parkinson Disease/pathology
• Parkinson Disease/metabolism
• Parkinson Disease/diagnosis
• Spinocerebellar Ataxias/pathology
• Spinocerebellar Ataxias/metabolism

• Alzheimer’s disease
• Anti-amyloid immunotherapy
• Clinical trial
• Disease-modifying therapy

• Alzheimer’s disease
• amyloid beta
• clinical trials
• monoclonal antibody
• passive immunotherapy

• Alzheimer Disease/metabolism
• Alzheimer Disease/therapy
• Humans
• Amyloid beta-Peptides/metabolism
• Plaque, Amyloid/metabolism
• Brain/metabolism
• Antibodies, Monoclonal, Humanized/therapeutic use
• Antibodies, Monoclonal, Humanized/pharmacology
• Amyloid/metabolism

• 81930028 National Natural Science Foundation of China (National Science Foundation of China)
• 82120108010 National Natural Science Foundation of China (National Science Foundation of China)

• Alzheimer's disease
• Anti-amyloid
• Anti-tau
• Clinical trials
• Neuroprotection
• Precision medicine.
• Tautopathy

• Alzheimer Disease/drug therapy
• Alzheimer Disease/diagnosis
• Alzheimer Disease/metabolism
• Humans
• Precision Medicine
• Cholinesterase Inhibitors/therapeutic use
• Cholinesterase Inhibitors/pharmacology
• Cholinesterase Inhibitors/chemistry
• Amyloid beta-Peptides/antagonists & inhibitors
• Amyloid beta-Peptides/metabolism

• Alzheimer’s disease
• cognition
• fatty acids
• high-fat diet
• metabolism
• neuropathology

• Mice
• Animals
• Alzheimer Disease/pathology
• Diet, High-Fat/adverse effects
• Amyloid beta-Peptides/metabolism
• Mice, Transgenic
• Disease Models, Animal
• Fatty Acids

• Alzheimer’s disease
• Amyloid cascade hypothesis
• Animal model
• Organoid

• Alzheimer Disease/metabolism
• Humans
• Animals
• Disease Models, Animal
• Organoids/metabolism
• Amyloid beta-Peptides/metabolism

• Alzheimer’s disease
• amyloid-β oligomers
• multi-target therapy
• transgenic mouse model

• Mice
• Animals
• Alzheimer Disease/genetics
• Alzheimer Disease/pathology
• Mice, Transgenic
• Amyloid beta-Protein Precursor/genetics
• Disease Models, Animal
• Thinking
• Amyloid beta-Peptides/genetics

• Alzheimer’s disease
• amyloid hypothesis
• amyloid-β
• antibodies
• clearance
• clinical trials
• downstream effects
• intravenous immunoglobulin

• AD
• Alzheimer’s disease
• antioxidants
• ellagic acid
• gut-microbial
• multifunctional compounds
• neuroprotection
• nutraceuticals
• pomegranate fruit
• urolithins

• Alzheimer’s disease
• amyloid β-protein
• amyloid β-protein precursor
• apolipoprotein E
• isoform
• low-density lipoprotein receptor

• Animals
• Humans
• Mice
• Alzheimer Disease/drug therapy
• Alzheimer Disease/genetics
• Alzheimer Disease/metabolism
• Amyloid beta-Peptides/metabolism
• Amyloid beta-Protein Precursor/metabolism
• Apolipoproteins E/antagonists & inhibitors
• Apolipoproteins E/genetics
• Cognition/drug effects
• Disease Models, Animal
• Mice, Transgenic
• Neuroprotective Agents/pharmacology
• Neuroprotective Agents/therapeutic use
• Peptide Fragments/pharmacology
• Peptide Fragments/therapeutic use

• Alzheimer’s disease
• Amyloid
• Clinical trial
• Disease-modifying therapy
• Preclinical

• Humans
• Alzheimer Disease/drug therapy
• Amyloid beta-Peptides/metabolism
• Immunotherapy/methods
• Brain/metabolism
• Positron-Emission Tomography

• K23 AG059888 NIA NIH HHS
• P01 AG019724 NIA NIH HHS
• T32 AG023481 NIA NIH HHS
• National Institutes of Health

• Alzheimer’s disease
• amyloid beta
• mouse model
• sleep deterioration
• tau

• Alzheimer’s disease
• Barrier dysfunction
• Barrier leakage
• Blood-brain barrier
• Cerebrovasculature
• Neurovasculature

• Alzheimer Disease/drug therapy
• Animals
• Biological Transport
• Blood-Brain Barrier/pathology
• Cognitive Dysfunction
• Disease Models, Animal
• Humans

• R01 AG039621 NIA NIH HHS
• R01 AG075583 NIA NIH HHS
• RF1 AG039621 NIA NIH HHS

• Alzheimer’s disease
• amyloid cascade hypothesis
• animal models
• biomarkers
• neurofibrillary tangles
• pharmacological intervention
• tau

• Alzheimer Disease/drug therapy
• Alzheimer Disease/metabolism
• Alzheimer Disease/pathology
• Amyloid beta-Protein Precursor/genetics
• Amyloid beta-Protein Precursor/metabolism
• Animals
• Biomarkers/metabolism
• Cognitive Dysfunction/metabolism
• Cognitive Dysfunction/pathology
• Disease Models, Animal
• Gene Knock-In Techniques
• Mice
• Mice, Transgenic
• tau Proteins/metabolism

• 19H03532, 19H05017, 19K21811, 20H01037 Grants-in-Aid for Scientific Research from MEXT
• non biomedical research from the SRF, Japan
• non the Takeda Science Foundation
• non the Mishima Kaiun Memorial Foundation
• non the Hori Sciences and Arts Foundation
• non the Strategic Research Program for Brain Science from the Japan Agency for Medical Research and Development (AMED)

Diverse gene products contribute to the pathogenesis of Alzheimer’s disease (AD). Experimental models have helped elucidate their mechanisms and impact on brain functions. Human amyloid precursor protein (hAPP) transgenic mice from line J20 (hAPP-J20 mice) are widely used to simulate key aspects of AD. However, they also carry an insertional mutation in noncoding sequence of one Zbtb20 allele, a gene involved in neural development. We demonstrate that heterozygous hAPP-J20 mice have reduced Zbtb20 expression in some AD-relevant brain regions, but not others, and that Zbtb20 levels are higher in hAPP-J20 mice than heterozygous Zbtb20 knock-out (Zbtb20^+/–) mice. Whereas hAPP-J20 mice have premature mortality, severe deficits in learning and memory, other behavioral alterations, and prominent nonconvulsive epileptiform activity, Zbtb20^+/– mice do not. Thus, the insertional mutation in hAPP-J20 mice does not ablate the affected Zbtb20 allele and is unlikely to account for the AD-like phenotype of this model.

• Alzheimer’s disease
• Zbtb20
• amyloid precursor protein
• behavior
• epilepsy
• mouse model

Alzheimer’s disease (AD) is a prevalent neurological disorder affecting memory function in elderly persons. Indeed, AD exhibits abnormality in cognitive behaviors and higher susceptibility to neuropsychiatric symptoms (NPS). Various factors including aging, sex difference and NPS severity, are implicated during in development of AD. In this study, we evaluated behavioral abnormalities of AD model, PDAPP transgenic mice at young age using the Morris Water Maze test, which was established to assess hippocampal-dependent learning and memory. We found that female AD model mice exhibited spatial learning dysfunction and highly susceptible to NPS such as anxiety and depression, whereas spatial reference memory function was comparable in female PDAPP Tg mice to female wild type (WT) mice. Spatial learning function was comparable in male AD model mice to male WT mice. Multiple regression analysis showed that spatial learning dysfunction was associated with NPS severity such as anxiety and depression. Furthermore, the analysis showed that spatial reference memory function was associated with status of depression, but not anxiety. Thus, these results suggest female dominance of spatial learning dysfunction in the AD model mice accompanying increased NPS severity. The understandings of AD model may be useful for the development of therapeutic agents and methods in human AD.

• Alzheimer’s disease model
• PDAPP Tg mice
• cognitive function
• correlation analysis
• neuropsychiatric symptom

Elderly patients with dementia suffer from cognitive dysfunctions and neuropsychiatric symptoms (NPS) such as anxiety and depression. Alzheimer’s disease (AD) is a form of age-related dementia, and loss of cholinergic neurons is intimately associated with development of AD symptoms. We and others have reported that neural cell transplantation ameliorated cognitive dysfunction in AD model mice. It remains largely unclear whether neural cell transplantation ameliorates the NPS of AD. It would be interesting to determine whether NPS correlates with cognitive dysfunctions before and after neural cell transplantation in AD model mice. Based on the revalidation of our previous data from a Morris water maze test, we found that neural cell transplantation improved anxiety and depression significantly and marginally affected locomotion activity in AD mice. A correlation analysis revealed that the spatial learning function of AD mice was correlated with their NPS scores both before and after cell transplantation in a similar manner. In contrast, in the mice subjected to cell transplantation, spatial reference memory function was not correlated with NPS scores. These results suggested the neural cell transplantation in the AD model mice significantly improved NPS to the same degree as cognitive dysfunctions, possibly via distinct mechanisms, such as the cholinergic and GABAergic systems.

• Alzheimer’s disease
• PDAPP Tg mice
• neural transplantation
• neuropsychiatric symptoms

The incidence of metabolic disorders, as well as of neurodegenerative diseases—mainly the sporadic forms of Alzheimer’s and Parkinson’s disease—are increasing worldwide. Notably, obesity, diabetes, and hypercholesterolemia have been indicated as early risk factors for sporadic forms of Alzheimer’s and Parkinson’s disease. These conditions share a range of molecular and cellular features, including protein aggregation, oxidative stress, neuroinflammation, and blood-brain barrier dysfunction, all of which contribute to neuronal death and cognitive impairment. Rodent models of obesity, diabetes, and hypercholesterolemia exhibit all the hallmarks of these degenerative diseases, and represent an interesting approach to the study of the phenotypic features and pathogenic mechanisms of neurodegenerative disorders. We review the main pathological aspects of Alzheimer’s and Parkinson’s disease as summarized in rodent models of obesity, diabetes, and hypercholesterolemia.

• Alzheimer’s disease
• Parkinson’s disease
• diabetes
• hypercholesterolemia
• neurodegeneration
• obesity
• rodent models

• Active and passive state in wakefulness
• Alzheimer’s disease
• TASTPM mice
• electroencephalography
• wild type mice

• Alzheimer's disease
• amyloid β-protein (Aβ)
• amyloid β-protein precursor (APP)
• gallic acid
• nonamyloidogenic
• phenolic compound
• plant
• secretase

• Alzheimer's disease
• amyloid β-protein
• long-term depression
• long-term potentiation
• soluble Aβ oligomers
• synaptic plasticity

• Alzheimer Disease/metabolism
• Amyloid beta-Peptides/toxicity
• Animals
• Brain Chemistry
• Humans
• Neuronal Plasticity/drug effects
• Signal Transduction/drug effects

• P01 AG036694 NIA NIH HHS
• P50 AG005134 NIA NIH HHS
• R01 AG027443 NIA NIH HHS

• Antibody drug
• Cognition
• Neurodegeneration
• Synaptic plasticity
• Therapy

• Alzheimer Disease/drug therapy
• Alzheimer Disease/immunology
• Alzheimer Disease/metabolism
• Amyloid beta-Peptides/antagonists & inhibitors
• Animals
• Antibodies, Monoclonal/pharmacology
• Cells, Cultured
• Cricetinae
• Disease Models, Animal
• Hippocampus/drug effects
• Hippocampus/metabolism
• Immunologic Factors/pharmacology
• Long-Term Potentiation
• Mice
• Mice, Transgenic
• Neuronal Plasticity
• Receptor, trkB/agonists
• Receptor, trkB/metabolism

• Alzheimer disease
• flavonoid
• amyloid precursor protein (APP)
• amyloid-beta (AB)
• secretase
• transgenic mice
• neuroinflammation
• oxidative stress
• nonamyloidogenic
• phenol
• plant
• polyphenol

• Alzheimer’s disease
• Exercise
• astrocytes
• microglia
• neuroinflammation

Chiang et al. show that combining two complementary approaches for Aβ reduction improved cognitive function in a mouse model of amyloidosis relative to either treatment alone. Efficacy corresponded with restoration of mTOR signaling, TFEB expression, and autophagic flux, suggesting additional targets for future polytherapy in AD.

Drug development for Alzheimer’s disease has endeavored to lower amyloid β (Aβ) by either blocking production or promoting clearance. The benefit of combining these approaches has been examined in mouse models and shown to improve pathological measures of disease over single treatment; however, the impact on cellular and cognitive functions affected by Aβ has not been tested. We used a controllable APP transgenic mouse model to test whether combining genetic suppression of Aβ production with passive anti-Aβ immunization improved functional outcomes over either treatment alone. Compared with behavior before treatment, arresting further Aβ production (but not passive immunization) was sufficient to stop further decline in spatial learning, working memory, and associative memory, whereas combination treatment reversed each of these impairments. Cognitive improvement coincided with resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of hyperactive mammalian target of rapamycin signaling. Computational modeling corroborated by in vivo microdialysis pointed to the reduction of soluble/exchangeable Aβ as the primary driver of cognitive recovery.

• EFAD
• animal models
• apolipoprotein E
• apolipoprotein E lipidation
• apolipoproteins
• behavior
• brain
• cerebrovascular dysfunction
• histopathology
• lipoproteins
• neuronal viability

• Alzheimer Disease/genetics
• Alzheimer Disease/metabolism
• Alzheimer Disease/pathology
• Alzheimer Disease/therapy
• Animals
• Apolipoprotein E4/blood
• Apolipoprotein E4/genetics
• Disease Models, Animal
• Humans
• Mice
• Mice, Transgenic
• Phenotype

• R21 AG044682 NIA NIH HHS
• R21 AG051233 NIA NIH HHS
• UH2 NS100127 NINDS NIH HHS
• National Institutes of Health

• Alzheimer's disease
• amyloid precursor protein (APP)
• amyloid-β (AB)
• anti-amyloidogenic
• ferulic acid
• neurodegenerative disease
• octyl gallate
• α-secretase
• β-secretase 1 (BACE1)

APOE genotype is the foremost genetic factor modulating β-amyloid (Aβ) deposition and risk of sporadic Alzheimer’s disease (AD). Here we investigated how APOE genotype influences response to anti-Aβ immunotherapy.

APP_SW/PS1_dE9 (APP) transgenic mice with targeted replacement of the murine Apoe gene for human APOE alleles received 10D5 anti-Aβ or TY11-15 isotype control antibodies between the ages of 12 and 15 months.

Anti-Aβ immunization decreased both the load of fibrillar plaques and the load of Aβ immunopositive plaques in mice of all APOE backgrounds. Although the relative reduction in parenchymal Aβ plaque load was comparable across all APOE genotypes, APP/ε4 mice showed the greatest reduction in the absolute Aβ plaque load values, given their highest baseline. The immunization stimulated phagocytic activation of microglia, which magnitude adjusted for the post-treatment plaque load was the greatest in APP/ε4 mice implying association between the ε4 allele and impaired Aβ phagocytosis. Perivascular hemosiderin deposits reflecting ensued microhemorrhages were associated with vascular Aβ (VAβ) and ubiquitously present in control mice of all APOE genotypes, although in APP/ε3 mice their incidence was the lowest. Anti-Aβ immunization significantly reduced VAβ burden but increased the number of hemosiderin deposits across all APOE genotypes with the strongest and the weakest effect in APP/ε2 and APP/ε3 mice, respectively.

Our studies indicate that APOE genotype differentially modulates microglia activation and Aβ plaque load reduction during anti-Aβ immunotherapy. The APOE ε3 allele shows strong protective effect against immunotherapy associated microhemorrhages; while, conversely, the APOE ε2 allele increases risk thereof.

The online version of this article (doi:10.1186/s13024-017-0156-1) contains supplementary material, which is available to authorized users.

• Alzheimer’s disease
• Apolipoprotein E
• Brain hemorrhages
• Microglia
• Neurodegeneration
• Therapy
• Vasculopathy
• β-amyloid

• cognition
• developmental milestones
• embryonic development
• trisomy 21

• Alzheimer
• COPI
• EWAS studies
• GWAS studies
• human genetic

Dementia, including Alzheimer’s disease, the 21^st Century epidemic, is one of the most significant social and health crises which has currently afflicted nearly 44 million patients worldwide and about new 7.7 million cases are reported every year. This portrays the unmet need towards better understanding of Alzheimer’s disease pathomechanisms and related research towards more effective treatment strategies. The review thus comprehensively addresses Alzheimer’s disease pathophysiology with an insight of underlying multicascade pathway and elaborates possible therapeutic targets- particularly anti-amyloid approaches, anti-tau approaches, acetylcholinesterase inhibitors, glutamatergic system modifiers, immunotherapy, anti-inflammatory targets, antioxidants, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors and insulin. In spite of extensive research leading to identification of newer targets and potent drugs, complete cure of Alzheimer’s disease appears to be an unreached holy grail. This can be attributed to their ineffective delivery across blood brain barrier and ultimately to the brain. With this understanding, researchers are now focusing on development of drug delivery systems to be delivered via suitable route that can circumvent blood brain barrier effectively with enhanced patient compliance. In this context, we have summarized current drug delivery strategies by oral, transdermal, intravenous, intranasal and other miscellaneous routes and have accentuated the future standpoint towards promising therapy ultimately leading to Alzheimer’s disease cure.

• Neurofibrillary tangles
• Alzheimer’s disease
• Dementia
• Amyloid β
• Tau
• Neurodegeneration
• Blood brain barrier
• Transdermal
• Nasal

• NMDA receptor
• actin
• basal forebrain
• beta-amyloid
• cholinergic
• mGluR

The deposition of the amyloid β protein (Aβ) in the brain is a hallmark of Alzheimer's disease (AD). Removal of Aβ by Aβ-antibody treatment has been developed as a potential treatment strategy against AD. First clinical trials showed neither a stop nor a reduction of disease progression. Recently, we have shown that the formation of soluble and insoluble Aβ aggregates in the human brain follows a hierarchical sequence of three biochemical maturation stages (B-Aβ stages). To test the impact of the B-Aβ stage on Aβ immunotherapy, we treated transgenic mice expressing human amyloid precursor protein (APP) carrying the Swedish mutation (KM670/671NL; APP23) with the Aβ-antibody β1 or phosphate-buffered saline (PBS) beginning 1) at 3 months, before the onset of dendrite degeneration and plaque deposition, and 2) at 7 months, after the start of Aβ plaque deposition and dendrite degeneration.

At 5 months of age, first Aβ aggregates in APP23 brain consisted of non-modified Aβ (representing B-Aβ stage 1) whereas mature Aβ-aggregates containing N-terminal truncated, pyroglutamate-modified Aβ_N3pE and phosphorylated Aβ (representing B-Aβ stage 3) were found at 11 months of age in both β1- and PBS-treated animals. Protective effects on commissural neurons with highly ramified dendritic trees were observed only in 3-month-old β1-treated animals sacrificed at 5 months. When treatment started at 7 months of age, no differences in the numbers of healthy commissural neurons were observed between β1- and PBS-treated APP23 mice sacrificed with 11 months.

Aβ antibody treatment was capable of protecting neurons from dendritic degeneration as long as Aβ aggregation was absent or represented B-Aβ stage 1 but had no protective or curative effect in later stages with mature Aβ aggregates (B-Aβ stage 3). These data indicate that the maturation stage of Aβ aggregates has impact on potential treatment effects in APP23 mice.

The online version of this article (doi:10.1186/s40478-015-0217-z) contains supplementary material, which is available to authorized users.

Reductions in hippocampal neurite complexity and synaptic plasticity are believed to contribute to the progressive impairment in episodic memory and the mild cognitive decline that occur particularly in the early stages of Alzheimer's disease (AD). Despite the functional and therapeutic importance for patients with AD, intervention to rescue or normalize dendritic elaboration and synaptic plasticity is scarcely provided. Here we show that overexpression of neuritin, an activity-dependent protein, promoted neurite outgrowth and maturation of synapses in parallel with enhanced basal synaptic transmission in cultured hippocampal neurons. Importantly, exogenous application of recombinant neuritin fully restored dendritic complexity as well as spine density in hippocampal neurons prepared from Tg2576 mice, whereas it did not affect neurite branching of neurons from their wild-type littermates. We also showed that soluble recombinant neuritin, when chronically infused into the brains of Tg2576 mice, normalized synaptic plasticity in acute hippocampal slices, leading to intact long-term potentiation. By revealing the protective actions of soluble neuritin against AD-related neural defects, we provide a potential therapeutic approach for patients with AD.

• APP
• TTA
• amyloid
• amyloid precursor protein
• oligomer
• tetracycline transactivator

• Alzheimer's disease
• Beta-amyloid
• Immunotherapy
• Neurofibrillary tangles
• Phosphorylated tau
• Tau

The goal of this review is to discuss how behavioral tests in mice relate to the pathological and neuropsychological features seen in human Alzheimer's disease (AD), and present a comprehensive analysis of the temporal progression of behavioral impairments in commonly used AD mouse models that contain mutations in amyloid precursor protein (APP). We begin with a brief overview of the neuropathological changes seen in the AD brain and an outline of some of the clinical neuropsychological assessments used to measure cognitive deficits associated with the disease. This is followed by a critical assessment of behavioral tasks that are used in AD mice to model the cognitive changes seen in the human disease. Behavioral tests discussed include spatial memory tests [Morris water maze (MWM), radial arm water maze (RAWM), Barnes maze], associative learning tasks (passive avoidance, fear conditioning), alternation tasks (Y-Maze/T-Maze), recognition memory tasks (Novel Object Recognition), attentional tasks (3 and 5 choice serial reaction time), set-shifting tasks, and reversal learning tasks. We discuss the strengths and weaknesses of each of these behavioral tasks, and how they may correlate with clinical assessments in humans. Finally, the temporal progression of both cognitive and non-cognitive deficits in 10 AD mouse models (PDAPP, TG2576, APP23, TgCRND8, J20, APP/PS1, TG2576 + PS1 (M146L), APP/PS1 KI, 5×FAD, and 3×Tg-AD) are discussed in detail. Mouse models of AD and the behavioral tasks used in conjunction with those models are immensely important in contributing to our knowledge of disease progression and are a useful tool to study AD pathophysiology and the resulting cognitive deficits. However, investigators need to be aware of the potential weaknesses of the available preclinical models in terms of their ability to model cognitive changes observed in human AD. It is our hope that this review will assist investigators in selecting an appropriate mouse model, and accompanying behavioral paradigms to investigate different aspects of AD pathology and disease progression.

• 3×TG-AD mice
• APP mice
• APP/PS1 mice
• Alzheimer's disease
• behavior
• cognition
• mouse models
• neuropsychological assessment

• Alzheimer's disease (AD)
• amyloid-beta (Aβ)
• angiography
• cerebral amyloid angiopathy (CAA)
• cerebral blood flow (CBF)
• magnetic resonance imaging (MRI)
• microscopy
• transgenic mice

• Alzheimer’s disease
• immunotherapy
• tau
• β-amyloid

• AD
• AFP
• AHP
• Alzheimer’s disease
• CRLBs
• Cramér-Rao Lower Bounds
• FID
• MRS
• N-acetylaspartate
• NAA
• WT
• adiabatic full-passage
• adiabatic half-passage
• free induction decay
• mIns
• magnetic resonance spectroscopy
• myo-inositol
• tCr
• total creatine, sum of creatine and phosphocreatine
• treatment detection
• wild-type

Memory dysfunction is a common complaint following heart surgery and may be related to a diffuse ischemic state induced by microemboli dislodged during the procedure. Ischemia can induce damage by a number of mechanisms, including oxidative stress. Because pomegranates contain a variety of polyphenols with antioxidant and other potentially beneficial effects, we tested whether supplementation with a pomegranate extract before and after heart surgery could protect against postoperative cognitive dysfunction. Patients undergoing elective coronary artery bypass graft and/or valve surgery were given either 2 g of pomegranate extract (in 2 POMx pills) or placebo (pills containing no pomegranate ingredients) per day from one week before surgery to 6 weeks after surgery. The patients were also administered a battery of neuropsychological tests to assess memory function at 1 week before surgery (baseline), 2 weeks after surgery, and 6 weeks after surgery. The placebo group had significant deficits in postsurgery memory retention, and the pomegranate treatment not only protected against this effect, but also actually improved memory retention performance for up to 6 weeks after surgery as compared to presurgery baseline performance.

• Adult
• Aged
• Aged, 80 and over
• Alzheimer Disease/cerebrospinal fluid
• Alzheimer Disease/diagnosis
• Amyloid/cerebrospinal fluid
• Amyloid beta-Peptides/cerebrospinal fluid
• Biomarkers/cerebrospinal fluid
• Case-Control Studies
• Cognitive Dysfunction/cerebrospinal fluid
• Cognitive Dysfunction/diagnosis
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Limit of Detection
• Male
• Middle Aged