• Amyloid
• Biomarkers
• Cerebrospinal fluid
• Idiopathic normal pressure hydrocephalus
• Plasma
• Serum
• tau

• Humans
• Hydrocephalus, Normal Pressure/diagnosis
• Hydrocephalus, Normal Pressure/blood
• Hydrocephalus, Normal Pressure/cerebrospinal fluid
• Hydrocephalus, Normal Pressure/surgery
• Biomarkers/blood
• Biomarkers/cerebrospinal fluid
• Prognosis
• Amyloid beta-Peptides/cerebrospinal fluid
• Amyloid beta-Peptides/blood
• tau Proteins/cerebrospinal fluid
• tau Proteins/blood
• Alzheimer Disease/diagnosis
• Alzheimer Disease/blood
• Alzheimer Disease/cerebrospinal fluid

• diffusion tensor imaging
• glymphopathy
• idiopathic normal pressure hydrocephalus
• immunoprecipitation
• lipocalin-type prostaglandin D synthase
• surface plasmon resonance
• tau
• western blotting

• Biomarkers
• CCL4
• Cerebrospinal fluid
• MCP-1
• Neuroinflammation
• Normal pressure hydrocephalus
• PD-L1
• Proteomics

• Humans
• Amyloid beta-Peptides
• Hydrocephalus, Normal Pressure/diagnosis
• tau Proteins
• Cytokines
• Neurodegenerative Diseases
• B7-H1 Antigen
• Biomarkers
• Alzheimer Disease

• 2021-02189 Vetenskapsrådet
• SG-22-0192 Svenska Sällskapet för Medicinsk Forskning
• Uppsala University

• Drug therapy
• Idiopathic normal pressure hydrocephalus
• Review
• Shunt surgery
• Treatable dementia

• Alzheimer’s disease
• beta amyloid
• biomarkers
• cerebrospinal fluid
• normal pressure hydrocephalus
• tau proteins
• vascular dementia

• Alzheimer’s disease
• MAPT
• MRNA marker
• TRPV4
• normal pressure hydrocephalus

Lumbar punctures are a common examination in the work-up of patients with idiopathic normal pressure hydrocephalus (iNPH) and cerebrospinal fluid (CSF) biomarkers should therefore be available for use in selection of shunt candidates. The aim of this study was to investigate if CSF biomarkers are associated with outcome after shunt surgery alone or in combination with comorbidity and imaging markers, and investigate associations between CSF biomarkers and symptoms.

Preoperative CSF biomarkers were analyzed in 455 patients operated with shunt surgery for iNPH at a single center during 2011–2018. Symptoms before and 12 months after shunt surgery were graded with the Swedish iNPH scale. Neurofilament light chain protein (NfL), total tau (T-tau), phosphorylated tau (P-tau) and amyloid beta1-42 (Aβ1-42) CSF levels were measured. Evans’ index and disproportionately enlarged subarachnoid space hydrocephalus were measured on preoperative CT-scans. Preoperative evaluation and follow-up 12 months after shunt surgery were available in 376 patients.

Higher levels of NfL and T-tau were associated with less improvement after shunt surgery (β = − 3.10, p = 0.016 and β = − 2.45, p = 0.012, respectively). Patients whose symptoms deteriorated after shunt surgery had higher preoperative levels of NfL (1250 ng/L [IQR:1020–2220] vs. 1020 [770–1649], p < 0.001) and T-tau (221 ng/L [IQR: 159–346] vs. 190 [135–261], p = 0.0039) than patients with postoperative improvement on the iNPH scale. Among the patients who improved ≥ 5 levels on the iNPH scale (55%), NfL was abnormal in 22%, T-tau in 14%, P-tau in 6% and Aβ1-42 in 45%, compared with normal reference limits. The inclusion of CSF biomarkers, imaging markers and comorbidity in multivariate predictive Orthogonal Projections to Latent Structures (OPLS) models to did not improve predictability in outcome after shunt surgery.

Higher levels of T-tau and NfL were associated with a less favorable response to shunt surgery, suggesting a more active neurodegeneration in this group of patients. However, CSF levels of these biomarkers can be elevated also in patients who respond to shunt surgery. Thus, none of these CSF biomarkers, alone or used in combination, are suitable for excluding patients from surgery.

The online version contains supplementary material available at 10.1186/s12987-022-00306-2.

• Amyloid beta
• Biomarkers
• Cerebrospinal fluid
• Lumbar puncture
• Neurofilament light chain
• Normal pressure hydrocephalus
• Tau

• clinical guideline
• diagnosis
• idiopathic normal pressure hydrocephalus
• management
• treatment

• Aged
• Aged, 80 and over
• Biomarkers/analysis
• Biomarkers/cerebrospinal fluid
• Cerebral Ventricles/diagnostic imaging
• Cerebral Ventricles/pathology
• Cerebrospinal Fluid Pressure
• Cerebrospinal Fluid Shunts/adverse effects
• Cerebrospinal Fluid Shunts/economics
• Cerebrospinal Fluid Shunts/methods
• Cerebrovascular Circulation
• Cognitive Dysfunction/diagnosis
• Cognitive Dysfunction/pathology
• Dementia/diagnosis
• Dementia/pathology
• Female
• Gait Disorders, Neurologic/diagnosis
• Gait Disorders, Neurologic/pathology
• Humans
• Hydrocephalus, Normal Pressure/classification
• Hydrocephalus, Normal Pressure/diagnosis
• Hydrocephalus, Normal Pressure/epidemiology
• Hydrocephalus, Normal Pressure/therapy
• Japan
• Magnetic Resonance Imaging
• Male
• Neuroimaging/methods
• Neurologic Examination
• Neuropsychological Tests
• Nuclear Medicine/methods
• Prognosis
• Subarachnoid Space/diagnostic imaging
• Subarachnoid Space/pathology
• Urinary Incontinence/diagnosis
• Urinary Incontinence/pathology

• CSF protein
• Normal pressure hydrocephalus
• alzheimer disease
• neurodegenerative disease
• shunt

• Alzheimer’s disease
• biomarkers
• cerebrospinal fluid
• normal pressure hydrocephalus
• vascular dementia

• Alzheimer’s disease
• Network meta-analysis
• Neurodegenerative diseases
• sAPPα
• sAPPβ

• Alzheimer Disease/cerebrospinal fluid
• Alzheimer Disease/diagnosis
• Amyloid beta-Protein Precursor/cerebrospinal fluid
• Female
• Humans
• Male
• Neurodegenerative Diseases/cerebrospinal fluid
• Solubility

Treating idiopathic normal pressure hydrocephalus (iNPH) with lumboperitoneal shunts (LPSs) may cause cerebrospinal fluid (CSF) overdrainage.

To investigate whether LPSs, including gravitational “add-on” and programmable pressure valves (PPVs/+GVs), reduce complications and improve outcomes.

We compared PPVs/+small lumen abdominal catheters (SLs) to PPVs/+GVs using different opening pressures for supine and standing positions. We analyzed 115 patients with iNPH in 2 consequent cohorts: 48 patients receiving LPSs with PPVs/+SLs and 67 patients receiving LPSs with PPVs/+GVs. The modified Rankin Scale (mRS), Japan iNPH grading scale, Mini Mental State Examination, Frontal Assessment Battery, and CSF biomarkers were evaluated.

Comparisons of postoperative clinical factors in 64 patients in the PPV/+SL and PPV/+GV groups using 1:1 propensity score matching revealed differences in the mean (±standard deviation) postoperative mRS (2.65 ± 1.07 vs 2.16 ± 1.02, P = .049) and gait disturbance scores (1.97 ± 1.03 vs 1.39 ± 0.92, P = .011). Thus, outcomes improved in the LPS group with the GV. Serious and nonserious adverse event rates for the PPV/+SL and PPV/+GV groups were 22.9% and 19.4% (P = .647) and 38% and 17.9% (P = .018), respectively, indicating higher rates of subdural collections for the PPV/+SL group.

This is the first study to examine LPS treatment for iNPH using a GV in tandem with a PPV. Our results suggest that the CSF shunt flow volume is restricted in the standing position and maintained in the supine position, thus improving iNPH symptoms. This may reduce intracranial CSF hypotension-related complications.

• Alzheimer’s disease
• CSF
• Multiple systems atrophy
• Parkinson’s disease
• Progressive supranuclear palsy
• biomarkers
• corticobasal degeneration
• frontotemporal dementia
• idiopathic normal pressure hydrocephalus
• vascular dementia

Idiopathic normal pressure hydrocephalus (iNPH) is commonly treated by cerebrospinal fluid (CSF) shunting. However, the long-term efficacy of shunt intervention in the presence of comorbid Alzheimer’s disease (AD) pathology is debated.

To identify AD-associated CSF biomarkers predictive of shunting surgery outcomes in patients with iNPH.

Preoperative levels of total and phosphorylated Tau (p-Tau) were measured in 40 patients with iNPH divided into low (<30 pg/mL) and high (≥30 pg/mL) p-Tau groups and followed up for three years after lumboperitoneal shunting. The modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), Frontal Assessment Battery, and iNPH Grading Scale scores were compared between the age-adjusted low (n = 24; mean age 75.7 years [SD 5.3]) and high (n = 11; mean age 76.0 years [SD 5.6]) p-Tau groups.

Cognitive function improved early in the low p-Tau group and was maintained thereafter (p = 0.005). In contrast, the high p-Tau group showed a gradual decline to baseline levels by the third postoperative year (p = 0.040). Although the p-Tau concentration did not correlate with the preoperative MMSE score, a negative correlation appeared and strengthened during follow-up (R² = 0.352, p < 0.001). Furthermore, the low p-Tau group showed rapid and sustained mRS grade improvement, whereas mRS performance gradually declined in the high p-Tau group.

Preoperative CSF p-Tau concentration predicted some aspects of cognitive function after shunt intervention in patients with iNPH. The therapeutic effects of shunt treatment were shorter-lasting in patients with coexisting AD pathology.

• Alzheimer’s disease
• cerebrospinal fluid shunt
• normal pressure hydrocephalus
• phosphorylation
• prognosis
• tau proteins

Secreted amyloid precursor protein-α (sAPPα) is a neuroprotective and memory-enhancing molecule, however, the mechanisms through which sAPPα promotes these effects are not well understood. Recently, we have shown that sAPPα enhances cell-surface expression of glutamate receptors. Activity-related cytoskeletal-associated protein Arc (Arg3.1) is an immediate early gene capable of modulating long-term potentiation, long-term depression and homeostatic plasticity through regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor localization. Accordingly, we hypothesized that sAPPα may enhance synaptic plasticity, in part, by the de novo synthesis of Arc. Using primary cortical and hippocampal neuronal cultures we found that sAPPα (1 nM, 2 h) enhances levels of Arc mRNA and protein. Arc protein levels were increased in both the neuronal somata and dendrites in a Ca²⁺/calmodulin-dependent protein kinase II-dependent manner. Additionally, dendritic Arc expression was dependent upon activation of mitogen-activated protein kinase and protein kinase G. The enhancement of dendritic Arc protein was significantly reduced by antagonism of N-methyl-D-aspartate (NMDA) and nicotinic acetylcholine (α7nACh) receptors, and fully eliminated by dual application of these antagonists. This effect was further corroborated in area CA1 of acute hippocampal slices. These data suggest sAPPα-regulated plasticity within hippocampal neurons is mediated by cooperation of NMDA and α7nACh receptors to engage a cascade of signal transduction molecules to enhance the transcription and translation of Arc.

• Alzheimer’s disease
• Arc/Arg3.1
• FUNCAT-PLA
• NMDA
• PKG
• plasticity
• sAPPα
• α7nACh

• biomarker
• cerebrospinal fluid
• idiopathic normal pressure hydrocephalus
• intracranial hypotension syndrome
• lipocalin-type prostaglandin D synthase
• transferrin

• Animals
• Brain/metabolism
• Humans
• Nervous System Diseases/cerebrospinal fluid
• Polysaccharides/metabolism
• Protein Isoforms/cerebrospinal fluid
• Protein Isoforms/chemistry
• Protein Isoforms/metabolism
• Transferrin/cerebrospinal fluid
• Transferrin/chemistry
• Transferrin/metabolism

• Aged
• Biomarkers/cerebrospinal fluid
• Blotting, Western
• Brain/metabolism
• Case-Control Studies
• Choroid Plexus/metabolism
• Cognition Disorders/rehabilitation
• Female
• Humans
• Hydrocephalus, Normal Pressure/metabolism
• Hydrocephalus, Normal Pressure/psychology
• Hydrocephalus, Normal Pressure/surgery
• Male
• Polysaccharides/metabolism
• Prognosis
• Transferrin/cerebrospinal fluid

• Amyloid-β 42
• cerebral amyloid burden
• glymphatic system
• normal pressure hydrocephalus
• phosphorylated tau
• tau protein

• Biomarker
• Cerebrospinal fluid leakage
• Intracranial hypotension syndrome
• Lipocalin-type prostaglandin D synthase
• Transferrin

Background: Patients presenting with the classical idiopathic normal pressure hydrocephalus (iNPH) triad often show additional parkinsonian spectrum signs. Accurate differential diagnosis strongly influences the long-term outcome of cerebrospinal fluid (CSF) shunting.

Objective: The aim of this study was to find potential CSF microRNA (miRNA) biomarkers for NPH mimics with parkinsonian syndromes that can reliably distinguish them from iNPH patients.

Methods: Two cohorts of 81 patients (cohort 1, n = 55; cohort 2, n = 26) with possible iNPH who were treated in two centers between January 2011 and May 2014 were studied. In both cohorts, CSF samples were obtained from patients clinically diagnosed with iNPH (n = 21 and n = 10, respectively), possible iNPH with parkinsonian spectrum (PS) (n = 18, n = 10, respectively), possible iNPH with Alzheimer’s disease (AD) (n = 16), and non-affected elderly individuals (NC) (n = 6). A three-step qRT-PCR analysis of the CSF samples was performed to detect miRNAs that were differentially expressed in the groups.

Results: The expression of hsa-miR-4274 in CSF was decreased in both cohorts of PS group patients (cohort 1: p < 0.0001, cohort 2: p < 0.0001), and was able to distinguish PS from iNPH with high accuracy (area under the curve = 0.908). The CSF concentration of hsa-miR-4274 also correlated with the specific binding ratio of ioflupane (¹²³I) dopamine transporter scan (r = –0.494, p = 0.044). By contrast, the level of hsa-miR-4274 was significantly increased in the PS group after CSF diversion.

Conclusion: Levels of CSF hsa-miR-4274 can differentiate PS from patients with iNPH, AD, and NC. This may be clinically useful for diagnostic purposes and predicting shunt treatment responses.

• Alzheimer’s disease
• cerebrospinal fluid
• idiopathic normal pressure hydrocephalus
• microRNAs
• parkinsonian syndrome

• CSF biomarkers
• Glymphatic system
• Idiopathic normal pressure hydrocephalus
• Neurodegenerative diseases

• Biomarkers
• adult
• hydrocephalus
• neurology
• neurosurgery

• Amyloid precursor protein
• Biomarker
• Cerebrospinal fluid
• Intraventricular hemorrhage
• L1CAM
• Neurosurgery
• Posthemorrhagic hydrocephalus
• Preterm
• sAPPα

The purpose of this systematic review and meta-analysis was to evaluate the performance of cerebrospinal fluid (CSF) beta amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) as potential diagnostic biomarkers for idiopathic normal-pressure hydrocephalus (iNPH) and to assess their utility indistinguishing patients with iNPH from those with Alzheimer disease (AD) and healthy normal controls.

Studies were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical Database, VIP Chinese database, and Chinese Bio-medicine Database (CBM) before August 2016. The standardized mean difference (SMD) and 95% confidence interval (CI), comparing CSF Aβ42, t-tau, and p-tau levels between iNPH, AD and healthy controls, were calculated using random-effects models. Subgroup analyses were created according to ethnicity (Caucasian or Asian) and CSF type (lumbar or ventricular), and the publication bias was estimated using Egger’s test and the Begg’s test.

A total of 10 studies including 413 patients with iNPH, 186 patients with AD and 147 healthy controls were included in this systematic review and meta-analysis. The concentrations of CSF t-tau, and p-tau were significantly lower in iNPH patients compared to AD (SMD = −1.26, 95% CI −1.95 to −0.57, P = 0.0004; SMD = −1.54, 95% CI −2.34 to −0.74, P = 0.0002, respectively) and lower than healthy controls (SMD = −0.80, 95% CI −1.50 to −0.09, P = 0.03; SMD = −1.12, 95% CI −1.38 to −0.86, P < 0.00001, respectively). Patients with iNPH had significantly lower Aβ42 levels compared with controls (SMD = −1.14, 95% CI −1.74 to −0.55, P = 0.0002), and slightly higher Aβ42 levels compared with AD patients (SMD = 0.32, 95% CI 0.00–0.63, P = 0.05). Subgroup analyses showed that the outcomes may have been influenced by ethnicity and CSF source. Compared to AD, overall sensitivity in differentiating iNPH was 0.813 (95% CI 0.636–0.928) for Aβ42, 0.828 (95% CI 0.732–0.900) for t-tau, 0.943 (95% CI 0.871–0.981) for p-tau. Relative to AD, overall specificity in differentiating iNPH was 0.506 (95% CI 0.393–0.619) for Aβ42, 0.842 (95% CI 0.756–0.907) for t-tau, 0.851 (95% CI 0.767–0.914) for p-tau.

The results of our meta-analysis suggest that iNPH may be associated with significantly reduced levels of CSF Aβ42, t-tau and p-tau compared to the healthy normal state. Compared to AD, both t-tau and p-tau were significantly decreased in iNPH, but CSF Aβ42 was slightly increased. Prospective studies are needed to further assess the clinical utility of these and other CSF biomarkers in assisting in the diagnosis of iNPH and differentiating it from AD and other neurodegenerative disorders.

The online version of this article (doi:10.1186/s12987-017-0062-5) contains supplementary material, which is available to authorized users.

• Alzheimer’s disease
• CSF biomarkers
• Idiopathic normal-pressure hydrocephalus
• Meta-analysis
• Systematic review

Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value.

CSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPPα, sAPPβ, Aβ₄₂), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC.

CSF levels of APP, sAPPα, sAPPβ, Aβ₄₂, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age (p<0.0001 and AUC = 0.99), followed by normalized sAPPβ (p = 0.0001, AUC = 0.95), tau, APP, and L1CAM. Among subjects ≤12 months, a normalized CSF sAPPα cut-point of 0.41 provided the best prediction of CHC (odds ratio = 528, sensitivity = 0.94, specificity = 0.97); these infants were 32 times more likely to have CHC.

CSF proteins such as sAPPα and related proteins hold promise as biomarkers of CHC in infants and young children, and provide insight into the pathophysiology of CHC during this critical period in neurodevelopment.

• Alzheimer's disease
• amyloid
• biomarker
• cerebrospinal fluid
• diagnosis

• APP
• Alzheimer's disease
• Aβ
• Tau
• aging
• biomarker
• cognitive impairment
• memory
• neurogenesis
• neuroprotection
• receptor
• sAPPα
• synaptic plasticity
• therapeutics

• Alzheimer Disease/metabolism
• Alzheimer Disease/therapy
• Amyloid beta-Peptides/metabolism
• Amyloid beta-Protein Precursor/metabolism
• Animals
• Brain/metabolism
• Disease Models, Animal
• Humans

• R01 AG032432 NIA NIH HHS
• R01 AG050253 NIA NIH HHS
• R01 AT007411 NCCIH NIH HHS
• R21 AG055116 NIA NIH HHS

• Alzheimer’s disease
• amyloid-β protein precursor
• gene expression profiling
• idiopathic normal pressure hydrocephalus
• transthyretin

Patients with idiopathic normal pressure hydrocephalus (iNPH) have reduced cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ) and α- and β-cleaved soluble forms of amyloid precursor protein (sAPPα and sAPPβ). The aims of this study were to examine if changes could also be seen in the CSF for secreted metabolites of APP-like protein 1 (APLP1) and to explore the prognostic value of amyloid-related CSF biomarkers, as well as markers of neuronal injury and astroglial activation, as regards to clinical outcome after shunt surgery.

Twenty patients diagnosed with iNPH, 10 improved and 10 unchanged by shunt surgery, and 20 neurologically healthy controls were included. All patients were examined clinically prior to surgery and at 6-month follow-up after surgery using the iNPH scale. Lumbar puncture was performed pre-operatively. CSF samples were analyzed for neurofilament light (NFL), Aβ isoforms Aβ38, Aβ40 and Aβ42, sAPPα, sAPPβ, APLP1 β-derived peptides APL1β25, APL1β 27 and APL1β 28 and YKL40 by immunochemical methods.

The concentrations of all soluble forms of APP, all Aβ isoforms and APL1β28 were lower, whilst APL1β25 and APL1β27 were higher in the CSF of iNPH patients compared to controls. There was no difference in biomarker concentrations between patients who improved after surgery and those who remained unchanged.

The reduced CSF concentrations of Aβ38, Aβ40, Aβ42, sAPPα and sAPPβ suggest that APP expression could be downregulated in iNPH. In contrast, APLP1 concentration in the CSF seems relatively unchanged. The increase of APL1β25 and APL1β27 in combination with a slight decreased APL1β28 could be caused by more available γ-secretase due to reduced availability of its primary substrate, APP. The data did not support the use of these markers as indicators of shunt responsiveness.

• APLP1
• Amyloid
• Cerebrospinal fluid
• NFL
• Neurodegeneration
• Normal pressure hydrocephalus
• Prediction
• YKL40

• Amyloid beta
• Biomarker
• Cognitive outcome
• Cystatin C
• Idiopathic normal pressure hydrocephalus
• Lipocalin-type prostaglandin D synthase
• Lumboperitoneal shunt

• CPC = choroid plexus cauterization
• DTI = diffusion tensor imaging
• ETV = endoscopic third ventriculostomy
• HCRN = Hydrocephalus Clinical Research Network
• ICP = intracranial pressure
• LPA = lysophosphatidic acid
• NIH = National Institutes of Health
• NPC = neural precursor cell
• NPH = normal pressure hydrocephalus
• NSC = neural stem cell
• National Institutes of Health
• PreOL = precursor oligodendroglia
• RCT = randomized controlled trial
• SVZ = subventricular zone
• TNF = tumor necrosis factor
• VP = ventriculoperitoneal
• VZ = ventricular zone
• conference
• hydrocephalus
• iNPH = idiopathic NPH
• research
• symposium

The aim of this study was to determine whether the improvement of cerebrospinal fluid (CSF) flow dynamics by CSF shunting, can suppress the oligomerization of amyloid β-peptide (Aβ), by measuring the levels of Alzheimer’s disease (AD)-related proteins in the CSF before and after lumboperitoneal shunting. Lumbar CSF from 32 patients with idiopathic normal pressure hydrocephalus (iNPH) (samples were obtained before and 1 year after shunting), 15 patients with AD, and 12 normal controls was analyzed for AD-related proteins and APLP1-derived Aβ-like peptides (APL1β) (a surrogate marker for Aβ). We found that before shunting, individuals with iNPH had significantly lower levels of soluble amyloid precursor proteins (sAPP) and Aβ38 compared to patients with AD and normal controls. We divided the patients with iNPH into patients with favorable (improvement ≥ 1 on the modified Rankin Scale) and unfavorable (no improvement on the modified Rankin Scale) outcomes. Compared to the unfavorable outcome group, the favorable outcome group showed significant increases in Aβ38, 40, 42, and phosphorylated-tau levels after shunting. In contrast, there were no significant changes in the levels of APL1β25, 27, and 28 after shunting. After shunting, we observed positive correlations between sAPPα and sAPPβ, Aβ38 and 42, and APL1β25 and 28, with shifts from sAPPβ to sAPPα, from APL1β28 to 25, and from Aβ42 to 38 in all patients with iNPH. Our results suggest that Aβ production remained unchanged by the shunt procedure because the levels of sAPP and APL1β were unchanged. Moreover, the shift of Aβ from oligomer to monomer due to the shift of Aβ42 (easy to aggregate) to Aβ38 (difficult to aggregate), and the improvement of interstitial-fluid flow, could lead to increased Aβ levels in the CSF. Our findings suggest that the shunting procedure can delay intracerebral deposition of Aβ in patients with iNPH.

• Aged
• Aged, 80 and over
• Alzheimer Disease/cerebrospinal fluid
• Alzheimer Disease/complications
• Amyloid beta-Peptides/cerebrospinal fluid
• Cerebrospinal Fluid Shunts/adverse effects
• Female
• Humans
• Hydrocephalus, Normal Pressure/complications
• Hydrocephalus, Normal Pressure/surgery
• Male
• Middle Aged

• LP shunt
• VP shunt
• biomarker
• idiopathic normal pressure hydrocephalus
• imaging
• prognosis

• Biomarkers/cerebrospinal fluid
• Diagnosis, Differential
• Diagnostic Imaging
• Diuretics/therapeutic use
• Early Diagnosis
• Humans
• Hydrocephalus, Normal Pressure/diagnosis
• Hydrocephalus, Normal Pressure/therapy
• Neuropsychological Tests
• Prognosis
• Sensitivity and Specificity
• Spinal Puncture
• Ventriculoperitoneal Shunt

• Biomarker
• Cerebrospinal fluid
• Normal pressure hydrocephalus
• Phosphorylated-tau
• Predictive value of tests
• β amyloid