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

摘要

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