Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer’s disease
Abstract
The enzyme β-secretase (BACE1) is essentially involved in the production of cerebral amyloidogenic pathology in Alzheimer's disease (AD). The measurement of BACE1 activity in cerebrospinal fluid (CSF) has been reported, which may render CSF measurement of BACE1 a potential biomarker candidate of AD. In order to investigate whether BACE1 protein activity is correlated with regional brain atrophy in AD, we investigated the association between CSF levels of BACE1 and MRI-assessed hippocampus volume in patients with AD (n = 30). An increase in CSF-BACE1 activity was associated with decreased left and right hippocampus volume corrected for global head volume in the AD patients. Boot-strapped regression analysis showed that increased CSF levels of BACE1 activity were associated with increased CSF concentration of total tau but not amyloid-β1-42 in AD. White matter hyperintensities did not influence the results. BACE1 activity and protein levels were significantly increased in AD compared to 19 elderly healthy controls. Thus, the CSF biomarker candidate of BACE1 activity was associated with hippocampus atrophy in AD in a robust manner and may reflect neurotoxic amyloid-β-related processes.
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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 [84]
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The β-Secretase BACE1 in Alzheimer’s Disease
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- Authors
- Ewers, M., Cheng, X., Zhong, Z., Nural, H. F., Walsh, C., Meindl, T., Teipel, S. J., Buerger, K., He, P., Shen, Y., & Hampel, H.
- Affiliations
- University of California, San Francisco (US)
- Shanghai Medical College of Fudan University (CN)
- Banner Sun Health Research Institute (US)
- Trinity College Dublin (IE)
- Ludwig-Maximilians-Universität München (DE)
- German Center for Neurodegenerative Diseases (DE)
- Alzheimer Memorial Center, Department of Psychiatry, Ludwig Maximilian University, Munich, Germany
- Goethe University Frankfurt (DE)
- Corresponding author
- Ewers, Michael
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2011-07-01
- Volume
- 25
- Issue
- 2
- Pages
- 373-381
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2158242781
- Cited by
- 58
- References
- 39
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 8 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 7
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- BACE1, beta-secretase
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Hippocampus, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Peptide Fragments, Linear Models, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, tau Proteins, Amyloid Precursor Protein Secretases
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