BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology
Abstract
Several studies have shown that reduced amyloid-beta 1-42 (Abeta(42)) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. beta-site APP cleaving enzyme (BACE1) is thought to be the major beta-secretase involved in Abeta production in the brain, and therefore we investigated the relation between BACE1 activity and CSF markers Abeta(40), Abeta(42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau) in CSF of control (n=12), mild cognitive impairment (n=18), and AD (n=17) subjects. Patients were classified according to their Abeta(42), t-tau, and p-tau CSF biomarker levels, with either an AD-like biomarker profile (two or three biomarkers abnormal: Abeta(42) < 495 pg/ml in combination with t-tau > 356 pg/ml, and/or p-tau > 54 pg/ml) or a normal biomarker profile (<or= one biomarker abnormal). This resulted in 19 subjects with an AD-like biomarker profile (66 +/- 6 years, 53% female, and Mini-Mental Status Examination (MMSE) score: 23 +/- 5) and 28 subjects with a normal biomarker profile (62 +/- 11 years, 43% female, and MMSE score: 27 +/- 4). Subjects with an AD-like biomarker profile had higher CSF BACE1 activity levels, compared to patients with a normal biomarker profile (20 pg/ml and 16 pg/ml respectively; p=0.01), when controlled for age and gender. In the whole sample, BACE1 activity correlated with CSF levels of Abeta(40), t-tau, and p-tau (r=0.38, r=0.63, and r=0.65; all p< 0.05), but not with Abeta(42). These data suggest that increased BACE1 activity in CSF relates to AD pathology in the brain.
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CSF BACE1 concentration and activity have good diagnostic performance in discriminating AD dementia, MCI, and cognitively healthy individuals.
“During the past 15 years, a few human in vivo studies reported good diagnostic performance of CSF BACE1 concentration (supposed to reflect gene expression levels) and activity in discriminating among patients with AD dementia, patients with MCI, and cognitively healthy individuals (79–85).”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [79]
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Zhang, Y., Wang, Y., & Zhao, F. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04743-6
“Among them, β-secretase, also known as β-site amyloid precursor protein cleaving enzyme 1 (BACE1), is the key enzyme for Aβ formation [11, 12].”
Rasadi, A., Sasani, S. T., & Ajamian, F. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05159-y
“BACE1 protein levels are upregulated in the AD brain and cerebrospinal fluid [29, 30], whereas reports on BACE1 mRNA levels in the AD brain are inconsistent.”
- Authors
- Mulder, S. D., van der Flier, W. M., Verheijen, J. H., Mulder, C., Scheltens, P., Blankenstein, M. A., Hack, C. E., & Veerhuis, R.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands
- Netherlands Organisation for Applied Scientific Research (NL)
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2010-03-24
- Volume
- 20
- Issue
- 1
- Pages
- 253-260
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1772512580
- Cited by
- 80
- References
- 0
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 3 · 2018: 9 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 11 · 2012: 5
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- TNO Repository (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Vanderbilt University Medical Center
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- BACE1
- MeSH terms
- Aged, Alzheimer Disease, Apolipoproteins E, Cognition Disorders, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Peptide Fragments, Statistics as Topic, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, tau Proteins, Amyloid Precursor Protein Secretases
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