Increased CSF-BACE 1 activity is associated with ApoE-ε4 genotype in subjects with mild cognitive impairment and Alzheimer's disease
Abstract
The Apolipoprotein (ApoE) epsilon 4 allele is a major genetic risk factor of Alzheimer's disease, and may affect the production of amyloid beta (A beta(1-42)). Recently, we have shown that beta-secretase (BACE 1) activity can be reliably detected within the brain and human CSF. Here, we have examined an association between the ApoE genotype and CSF-levels of BACE 1 activity in Alzheimer's disease and mild cognitive impairment (MCI). A total of 148 subjects were included: 60 Alzheimer's disease patients, 51 MCI subjects and 37 elderly healthy controls. The CSF-levels of A beta(1-42), BACE 1 activity and BACE protein were measured in all of these subjects. The differences between ApoE-epsilon 4 carriers and ApoE-epsilon 4 non-carriers in these CSF-based measures were determined controlling for gender, age and MMSE score. The ApoE-epsilon 4 genotype was associated with increased BACE 1 activity in both Alzheimer's disease (P = 0.03) and MCI (P = 0.04) subjects. Levels of A beta(1-42) were decreased in ApoE-epsilon 4 carriers in MCI (P = 0.004) but not Alzheimer's disease subjects. This study is the first to demonstrate the association between ApoE-epsilon 4 and CSF-BACE 1 activity in MCI and Alzheimer's disease subjects. The assessment of BACE 1 in CSF may provide a sensitive measure to detect in vivo alterations in the amyloidogenic processing potentially modified by the ApoE genotype.
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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 [81]
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- Authors
- Ewers, M., Zhong, Z., Bürger, K., Wallin, A., Blennow, K., Teipel, S. J., Shen, Y., & Hampel, H.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Trinity College Dublin (IE)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-03-11
- Volume
- 131
- Issue
- 5
- Pages
- 1252-1258
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2019082497
- Cited by
- 119
- References
- 52
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 3 · 2022: 2 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 9 · 2012: 8
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG025888)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- APOE ε4, cerebrospinal fluid, mild cognitive impairment, Alzheimer's disease, amyloid-beta 42, amyloidogenic processing, genetic risk factors, biomarkers
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Cognition Disorders, Female, Genotype, Humans, Male, Middle Aged, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid Precursor Protein Secretases
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