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Cerebrospinal fluid Aβ42 is the best predictor of clinical progression in patients with subjective complaints
Open accessAbstract
Background: The need to recognize Alzheimer's disease (AD) as early as possible led us to evaluate the predictive value of amyloid β(1‐42) (Aβ42), total tau (tau), and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) for clinical progression in patients with subjective complaints. Methods: We recruited nondemented patients with subjective complaints (i.e., criteria for mild cognitive impairment [MCI] not fulfilled) from our memory clinic. We assessed the predictive value of CSF Aβ42, tau, and ptau for clinical progression using Cox proportional hazards models adjusted for age, gender, and baseline findings on the Mini‐Mental State Examination (MMSE). Clinical progression was defined as progression to MCI or AD. Results: We included 127 patients with subjective complaints (age 60 ± 10 years, 61 [48%] females, MMSE 29 ± 1). At baseline, Aβ42 and tau were abnormal in 20 patients (both 16%), and ptau in 32 patients (25%). Thirteen patients (10%) progressed to MCI (n = 11) or AD (n = 2). Aβ42 was the strongest predictor of progression to MCI or AD with an adjusted hazard ratio (HR) of 16.0 (3.8–66.4). The adjusted HR associated with tau was 2.8 (0.9–9.2) and with ptau 2.6 (0.8–8.2). Combinations of biomarkers had a lower predictive value than Aβ42 alone. Conclusion: Low Aβ42 was the strongest predictor of clinical progression in patients with subjective complaints. These results are in line with the hypothesis that the cascade of pathologic events starts with deposition of Aβ42, whereas neuronal degeneration and hyperphosphorylation of tau are more downstream events, closer to clinical manifestation of AD.
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Metadata
- Authors
- van Harten, A. C., Visser, P. J., Pijnenburg, Y. A. L., Teunissen, C. E., Blankenstein, M. A., Scheltens, P., & van der Flier, W. M.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Maastricht University Medical Centre (NL)
- Corresponding author
- van Harten, Argonde C.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2012-12-10
- Volume
- 9
- Issue
- 5
- Pages
- 481-487
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2013751858
- Cited by
- 197
- References
- 43
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 11 · 2023: 11 · 2022: 5 · 2021: 11 · 2020: 19 · 2019: 20 · 2018: 23 · 2017: 20 · 2016: 16 · 2015: 20 · 2014: 19 · 2013: 9
- FWCI
- 10.97
- Type
- journal article
- Language
- en
- Open access
- green
- research.vu.nl
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Alzheimer Nederland and Stichting VUmc Fonds
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, amyloid-beta 42
- MeSH terms
- Alzheimer Disease, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Biomarkers, Proportional Hazards Models, Amyloid beta-Peptides, tau Proteins, Disease Progression, Early Diagnosis, Cognitive Dysfunction
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