Increased plasma beta-secretase 1 may predict conversion to Alzheimer’s disease dementia in individuals with mild cognitive impairment
Open accessAbstract
Background Increased beta-secretase 1 (BACE1) activity has consistently been detected in brain tissue and cerebrospinal fluid of subjects with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) compared with control subjects. The collection of cerebrospinal fluid by lumbar puncture is invasive. We sought to identify the presence of plasma BACE1 activity and determine potential alterations in subjects with MCI with clinical follow-up examinations for 3 years using patients with diagnosed probable AD dementia compared with healthy control subjects.Methods Seventy-five patients with probable AD, 96 individuals with MCI, and 53 age-matched and sex-matched healthy control subjects were recruited from three independent international academic memory clinics and AD research expert centers. Plasma BACE1 activity was measured by a synthetic fluorescence substrate enzyme-linked immunosorbent assay. BACE1 protein expression was assessed by Western blotting using three different antibodies that recognize the epitopes of the N-terminus, C-terminus, and full-length BACE1.Results Compared with healthy control subjects, plasma BACE1 activity (V max) significantly increased by 53.2% in subjects with MCI and by 68.9% in patients with probable AD. Subjects with MCI who converted to probable AD dementia at follow-up examinations exhibited significantly higher BACE1 activity compared with cognitively stable MCI nonconverters and showed higher levels of BACE1 activity than patients with AD.Conclusions Plasma BACE1 activity is significantly increased in MCI converters and patients with probable AD. The sensitivities and specificities of BACE1 activity for the patients were 84% and 88%, respectively. Our results indicate that plasma BACE1 activity may be a biomarker for AD risk and could predict progression from prodromal to probable AD dementia.
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Plasma BACE1 activity has good diagnostic performance in discriminating AD dementia from MCI and cognitively normal individuals.
“In particular, plasma BACE1 activity demonstrated good diagnostic performance in discriminating patients with AD dementia from patients with MCI and cognitively normal individuals (87).”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [87]
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- [51]Shen Y He P Cheng X Ewers M Sabbagh M Lehe T Plasma BACE1 levels are increased in patients of mild cognitive impairment and Alzheimer’s disease 2011 Alzheimer’s Association 13th International Conference on Alzheimer’s Disease and Related Disorders Paris, France
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- Authors
- Shen, Y., Wang, H., Sun, Q., Yao, H., Keegan, A. P., Mullan, M., Wilson, J., Lista, S., Leyhe, T., Laske, C., Rujescu, D., Levey, A., Wallin, A., Blennow, K., Li, R., & Hampel, H.
- Affiliations
- University of Science and Technology of China (CN)
- Roskamp Institute (US)
- Arizona State University (US)
- Centre National de la Recherche Scientifique (FR)
- University Hospital of Basel (CH)
- Universitätsklinikum Tübingen (DE)
- Ludwig-Maximilians-Universität München (DE)
- Emory University (US)
- Sahlgrenska University Hospital (SE)
- Capital Medical University (CN)
- Corresponding author
- Li, Rena
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 83
- Issue
- 5
- Pages
- 447-455
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC5656540
- OpenAlex
- W2588851304
- Cited by
- 123
- References
- 54
- Citations by year
- 2026: 4 · 2025: 16 · 2024: 14 · 2023: 7 · 2022: 19 · 2021: 22 · 2020: 12 · 2019: 15 · 2018: 12 · 2017: 2
- FWCI
- 9.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- Fondation pour la Recherche sur la Biodiversite (ANR-10-IAIHU-06)
- American Health Assistance Foundation (G2006-118)
- Université Pierre et Marie Curie
- Hill, Holliday, Connors, Cosmopulos
- Key Technologies Research and Development Program
- Agence Nationale de la Recherche (Hospitalo-Universitaire-6)
- AXA Research Fund
- Ministry of Science and Technology of the People's Republic of China (2016YFC1300500-03)
- National Institute on Aging (NIHR01AG032441-01, NIHR21 AG049237, RO1AG025888)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- beta-secretase 1, BACE1, plasma biomarkers, mild cognitive impairment, Alzheimer's disease, conversion to dementia, disease progression prediction, sensitivity and specificity, amyloid-beta
- MeSH terms
- Aged, Alzheimer Disease, Female, Follow-Up Studies, Humans, Male, Prognosis, Sensitivity and Specificity, Biomarkers, Aspartic Acid Endopeptidases, Disease Progression, Amyloid Precursor Protein Secretases, Cognitive Dysfunction, Prodromal Symptoms
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