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