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

ABSTRACT

ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1) plays an important role in the development of Alzheimer's disease (AD), freeing the amyloid-ß (Aß) N-terminus from the amyloid-ß protein precursor (AßPP), the first step in Aß 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 sAßPPß, the N-terminal secreted product of BACE1 (sBACE1) activity on AßPP. Here, sBACE1 enzymatic activity and secreted AßPPß (sAßPPß) 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 sAßPPß demonstrated a moderate yet significant degree of correlation with each other, there was no correlation of either analyte to CSF Aß peptide ending at residue 42. Surprisingly, a stronger correlation was demonstrated between CSF sBACE1 activity and tau, which was comparable to that between CSF Aß42 and tau. Unlike for these latter two analytes, receiver-operator characteristic curves demonstrate that neither CSF sBACE1 activity nor sAßPPß concentrations can be used to differentiate between healthy elderly and AD individuals.