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Elevated Cerebrospinal Fluid BACE1 Activity in Incipient Alzheimer Disease
Abstract
BACKGROUND: We used a sensitive and specific beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) assay to determine the relationship between BACE1 activity in cerebrospinal fluid (CSF) and markers of APP metabolism and axonal degeneration in early and late stages of Alzheimer disease (AD). OBJECTIVE: To assess CSF BACE1 activity in AD. DESIGN: Case-control and longitudinal follow-up study. SETTING: Specialized memory clinic. Patients Eighty-seven subjects with AD, 33 cognitively normal control subjects, and 113 subjects with mild cognitive impairment (MCI), who were followed up for 3 to 6 years. MAIN OUTCOME MEASURES: Cerebrospinal fluid BACE1 activity in relation to diagnosis and CSF levels of secreted APP and amyloid beta protein (Abeta) isoforms and the axonal degeneration marker total tau. RESULTS: Subjects with AD had higher CSF BACE1 activity (median, 30 pM [range, 11-96 pM]) than controls (median, 23 pM [range, 8-43 pM]) (P =.02). Subjects with MCI who progressed to AD during the follow-up period had higher baseline BACE1 activity (median, 35 pM [range, 18-71 pM]) than subjects with MCI who remained stable (median, 29 pM [range, 14-83 pM]) (P < .001) and subjects with MCI who developed other forms of dementia (median, 20 pM [range, 10-56 pM]) (P <.001). BACE1 activity correlated positively with CSF levels of secreted APP isoforms and Abeta(40) in the AD and control groups and in all MCI subgroups (P < .05) except the MCI subgroup that developed AD. Strong positive correlations were found between CSF BACE1 activity and total tau levels in all MCI subgroups (r >or= 0.57, P
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“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 [83]
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Metadata
- Authors
- Zetterberg, H., Andreasson, U., Hansson, O., Wu, G., Sankaranarayanan, S., Andersson, M. E., Buchhave, P., Londos, E., Umek, R. M., Minthon, L., Simon, A. J., & Blennow, K.
- Affiliations
- University of Gothenburg (SE)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2008-08-01
- Volume
- 65
- Issue
- 8
- Pages
- 1102-7
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2117635180
- Cited by
- 224
- References
- 23
- Citations by year
- 2025: 4 · 2024: 8 · 2023: 6 · 2022: 12 · 2021: 11 · 2020: 9 · 2019: 11 · 2018: 18 · 2017: 7 · 2016: 10 · 2015: 20 · 2014: 15 · 2013: 26 · 2012: 21
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- cerebrospinal fluid, Alzheimer's disease, mild cognitive impairment, amyloid precursor protein, amyloid-beta, total tau, axonal degeneration, APP metabolism, biomarkers, disease progression
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Axons, Enzyme Activation, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Nerve Degeneration, Biomarkers, Case-Control Studies, Aspartic Acid Endopeptidases, Amyloid Precursor Protein Secretases
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