Levels of β-Secretase (BACE1) in Cerebrospinal Fluid as a Predictor of Risk in Mild Cognitive Impairment
Abstract
CONTEXT: Elevated beta-secretase (beta-site amyloid precursor protein-cleaving enzyme 1 [BACE1]) activity has been found in the brains of patients with sporadic Alzheimer disease (AD) compared with controls. Now we are particularly interested in whether BACE1 can be identified in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI), a population at high risk for AD. The possible presence of BACE1 in the CSF of patients with AD and MCI has so far gone unreported. OBJECTIVE: To examine whether BACE1 can be identified in the CSF of patients with MCI. DESIGN: We evaluated CSF BACE1 levels using 2 sandwich enzyme-linked immunosorbent assays, BACE1 enzymatic activities by means of synthetic fluorescence substrate, and total amyloid-beta peptide levels using a sandwich enzyme-linked immunosorbent assay. SETTING: Two independent research centers. PARTICIPANTS: Eighty patients with sporadic AD, 59 patients with MCI, and 69 controls. MAIN OUTCOME MEASURES: BACE1 levels and enzymatic activities and amyloid-beta peptide levels. RESULTS: Increased CSF levels of BACE1 protein were associated with increased risk ratios (RRs) for patients with MCI compared with controls (RR, 2.08; 95% confidence interval [CI], 1.58-2.58) and patients with AD (RR, 1.65; 95% CI, 1.19-2.03). Similarly, patients with MCI showed increased levels of BACE1 activity compared with controls (RR, 2.17; 95% CI, 1.66-2.71) and patients with AD (RR, 3.71; 95% CI, 2.74-4.36). For total amyloid-beta peptide and tau, increased CSF levels were associated with a higher risk of MCI compared with controls. The BACE1 activity was significantly correlated with BACE1 protein level (rho = 0.23; P<.001) and amyloid-beta peptide level (rho = 0.39; P<.001), with amyloid-beta peptide correlated with BACE1 protein level (rho = 0.30; P<.001). CONCLUSION: Significant elevation of BACE1 levels and activity in CSF is an indicator of MCI, which could be an early stage of AD.
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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 [80]
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- Authors
- Zhong, Z., Ewers, M., Teipel, S., Bürger, K., Wallin, A., Blennow, K., He, P., McAllister, C., Hampel, H., & Shen, Y.
- Affiliations
- Banner Sun Health Research Institute (US)
- Ludwig-Maximilians-Universität München (DE)
- University of Gothenburg (SE)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2007-06-01
- Volume
- 64
- Issue
- 6
- Pages
- 718
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2001032146
- Cited by
- 206
- References
- 48
- Citations by year
- 2025: 8 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 11 · 2019: 9 · 2018: 13 · 2017: 5 · 2016: 5 · 2015: 12 · 2014: 12 · 2013: 19 · 2012: 17
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG025888, AG025888)
- 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
- beta-secretase, BACE1, cerebrospinal fluid biomarkers, mild cognitive impairment, Alzheimer's disease, amyloid-beta, tau protein, risk prediction, sporadic Alzheimer's disease, biomarker discovery, sandwich ELISA
- MeSH terms
- Alzheimer Disease, Brain, Cognition Disorders, Enzyme-Linked Immunosorbent Assay, Humans, Risk Factors, Severity of Illness Index, Blotting, Western, Aspartic Acid Endopeptidases, tau Proteins, Amyloid Precursor Protein Secretases
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