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

Mary J Savage; Daniel J Holder; Guoxin Wu; June Kaplow; Judith A Siuciak; William Z Potter; Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium CSF Proteomics Project Team for the Alzheimer’s Disease Neuroimaging Initiative

doi:10.3233/JAD-142778

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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

Journal article

Open access

Peer reviewed

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

Mary J Savage, Daniel J Holder, Guoxin Wu, June Kaplow, Judith A Siuciak, William Z Potter and Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium CSF Proteomics Project Team for the Alzheimer’s Disease Neuroimaging Initiative

Journal of Alzheimer's disease, Vol.46(2), pp.431-440

2015

DOI: 10.3233/JAD-142778

PMCID: PMC6287641

PMID: 25790831

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https://www.ncbi.nlm.nih.gov/pmc/articles/6287641View

Open Access

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.

Neuroimaging

Peptide Fragments - cerebrospinal fluid

Humans

Middle Aged

Male

tau Proteins - cerebrospinal fluid

Alzheimer Disease - cerebrospinal fluid

Amyloid Precursor Protein Secretases - cerebrospinal fluid

Case-Control Studies

Alzheimer Disease - diagnosis

Aspartic Acid Endopeptidases - cerebrospinal fluid

Amyloid beta-Protein Precursor - cerebrospinal fluid

Aged, 80 and over

Amyloid beta-Peptides - cerebrospinal fluid

Female

ROC Curve

Aged

Biomarkers - cerebrospinal fluid

Details

Title: Subtitle: 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
Creators: Mary J Savage - Merck and Company, West Point, PA, USA
Daniel J Holder - Merck and Company, West Point, PA, USA
Guoxin Wu - Merck and Company, West Point, PA, USA
June Kaplow - Eisai, Woodcliff Lake, NJ, USA
Judith A Siuciak - National Institute of Mental Health, Bethesda, MD, USA
William Z Potter - Philadelphia University
Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium CSF Proteomics Project Team for the Alzheimer’s Disease Neuroimaging Initiative
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: Journal of Alzheimer's disease, Vol.46(2), pp.431-440
DOI: 10.3233/JAD-142778
PMID: 25790831
PMCID: PMC6287641
NLM abbreviation: J Alzheimers Dis
ISSN: 1387-2877
eISSN: 1875-8908
Publisher: Netherlands
Grant note: Canadian Institutes of Health Research U01 AG024904 / NIA NIH HHS P30 AG013846 / NIA NIH HHS
Language: English
Date published: 2015
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984051724202771

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