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 of Alzheimer's Disease : JAD
Mary J SavageFoundation for National Institutes of Health (FNIH) Biomarkers Consortium CSF Proteomics Project Team for Alzheimer's Diseas

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 demonst...Continue Reading

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Citations

Jul 10, 2016·Journal of Alzheimer's Disease : JAD·Ann De VosEugeen Vanmechelen
Jul 22, 2015·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Enchi LiuAdam J Schwarz
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May 13, 2018·BMC Medical Genetics·Hao HuUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Jul 11, 2019·Molecular Neurobiology·Inmaculada Lopez-FontJavier Sáez-Valero
Jul 16, 2020·Journal of Personalized Medicine·Chiara VillaRomina Combi
Nov 1, 2016·Personalized Medicine·Patricia Regina ManzineMárcia Regina Cominetti
Jan 4, 2020·Therapeutic Advances in Neurological Disorders·Marta Milà-AlomàJosé Luís Molinuevo
Apr 5, 2017·Journal of Alzheimer's Disease : JAD·Inmaculada Lopez-FontJavier Sáez-Valero
Nov 30, 2018·Acta Neuropathologica·José Luis MolinuevoKaj Blennow
Oct 18, 2020·Alzheimer's Research & Therapy·Harald HampelUNKNOWN Alzheimer’s Precision Medicine Initiative (APMI)
Feb 14, 2021·Brain Sciences·Donovan A McGrowderRuby Alexander-Lindo
Apr 1, 2020·Biological Psychiatry·Harald HampelAndrea Vergallo

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