Dataset Information

Soluble BACE-1 Activity and sA?PP? Concentrations in Alzheimer's Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer's Disease Neuroimaging Initiative-1 Baseline Cohort.

ABSTRACT: ?-site amyloid precursor protein-cleaving enzyme 1 (BACE1) plays an important role in the development of Alzheimer's disease (AD), freeing the amyloid-? (A?) N-terminus from the amyloid-? protein precursor (A?PP), the first step in A? formation. Increased BACE1 activity in AD brain or cerebrospinal fluid (CSF) has been reported. Other studies, however, found either no change or a decrease with AD diagnosis in either BACE1 activity or sA?PP?, the N-terminal secreted product of BACE1 (sBACE1) activity on A?PP. Here, sBACE1 enzymatic activity and secreted A?PP? (sA?PP?) were measured in Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) baseline CSF samples and no statistically significant changes were found in either measure comparing healthy control, mild cognitively impaired, or AD individual samples. While CSF sBACE1 activity and sA?PP? demonstrated a moderate yet significant degree of correlation with each other, there was no correlation of either analyte to CSF A? peptide ending at residue 42. Surprisingly, a stronger correlation was demonstrated between CSF sBACE1 activity and tau, which was comparable to that between CSF A??? and tau. Unlike for these latter two analytes, receiver-operator characteristic curves demonstrate that neither CSF sBACE1 activity nor sA?PP? concentrations can be used to differentiate between healthy elderly and AD individuals.

SUBMITTER: Savage MJ

PROVIDER: S-EPMC6287641 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Soluble BACE-1 Activity and sAβPPβ Concentrations in Alzheimer's Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer's Disease Neuroimaging Initiative-1 Baseline Cohort.

Savage Mary J MJ Holder Daniel J DJ Wu Guoxin G Kaplow June J Siuciak Judith A JA Potter William Z WZ

Journal of Alzheimer's disease : JAD 20150101 2

β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) plays an important role in the development of Alzheimer's disease (AD), freeing the amyloid-β (Aβ) N-terminus from the amyloid-β protein precursor (AβPP), the first step in Aβ formation. Increased BACE1 activity in AD brain or cerebrospinal fluid (CSF) has been reported. Other studies, however, found either no change or a decrease with AD diagnosis in either BACE1 activity or sAβPPβ, the N-terminal secreted product of BACE1 (sBACE1) acti ...[more]

PMID: 25790831

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Project description:The ADNI (Alzheimer's Disease Neuroimaging Initiative) is a large longitudinal study of patients with probable Alzheimer's disease (AD), patients with mild cognitive impairment (MCI) and healthy elderly controls followed for at least 2-3 years. Many participants in the ADNI are being treated with medications, and these may have beneficial or deleterious effects.The goal of the study was to characterize baseline medication use in the ADNI.Diagnosis, demographics, medication status, psychometric data and MRI measures of hippocampal volume and entorhinal cortex thickness were obtained for 818 participants from the ADNI cohort. Total number of medications, Beers list (potentially dangerous) medications and AD treatments were also tabulated. ANOVA and logistic regression were used to assess associations between baseline pharmacotherapy and diagnosis, demographics, and selected clinical and MRI variables.Of the 818 enrolled ADNI participants, 809 were available for analysis in the present study, including 184 patients with AD, 399 patients with MCI and 226 healthy elderly controls. Significant gender differences in recruitment were observed in the MCI group. The average number of medications per participant was 8 (SD 4) and 22% reported treatment with one or more Beers list medications. For symptomatic treatment of MCI or AD, donepezil and memantine were the most commonly reported drugs. As expected, MCI and AD patients with more severe impairment were more likely to be treated. Men received treatment more frequently than women. Older subjects and those with less education were less likely to receive treatment.AD and MCI participants from the ADNI cohort were being treated with polypharmacy and many were also taking one or more medications with the potential for adverse effects. Off-label use of cholinesterase inhibitors and/or memantine for MCI was common, with more severely affected patients most likely to receive treatment. Differences in the frequency of symptomatic treatment were also observed as a function of age, years of education, gender and disease severity.

Project description:Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aβ) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aβ1-42, Aβ1-40, Aβ1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99mTc-ethyl cysteinate dimer single photon emission computerized tomography (99mTc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11C-labeled Pittsburgh Compound B-positron emission tomography (11C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aβ1-38, Aβ1-40, Aβ1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant.

Dataset Information

Soluble BACE-1 Activity and sA?PP? Concentrations in Alzheimer's Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer's Disease Neuroimaging Initiative-1 Baseline Cohort.

Publications

Soluble BACE-1 Activity and sAβPPβ Concentrations in Alzheimer's Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer's Disease Neuroimaging Initiative-1 Baseline Cohort.

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