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
Affiliations: [a] Merck and Company, West Point, PA, USA | [b] Eisai, Woodcliff Lake, NJ, USA | [c] National Institute of Mental Health, Bethesda, MD, USA
Correspondence:
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Correspondence to: Mary J. Savage, Molecular Biomarkers & Diagnostics, Merck Research Laboratories, RY50-1D-131, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. Tel.: +1 732 594 1089; mary_savage@merck.com
Note: [1] Data used in preparation of this article were obtained fromthe Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu/). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of thisreport. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Abstract: 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) activity on AβPP. Here, sBACE1 enzymatic activity and secreted AβPPβ (sAβPPβ) 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 sAβPPβ demonstrated a moderate yet significant degree of correlation with each other, there was no correlation of either analyte to CSF Aβ peptide ending at residue 42. Surprisingly, a stronger correlation was demonstrated between CSF sBACE1 activity and tau, which was comparable to that between CSF Aβ42 and tau. Unlike for these latter two analytes, receiver-operator characteristic curves demonstrate that neither CSF sBACE1 activity nor sAβPPβ concentrations can be used to differentiate between healthy elderly and AD individuals.
