Plasma Aβ40 and Aβ42 and Alzheimer’s disease: Relation to age, mortality, and risk
Abstract
BACKGROUND: Plasma amyloid [beta]-peptide (A[beta]) 40 and A[beta]42 levels are increased in persons with mutations causing early-onset familial Alzheimer's disease (AD). Plasma A[beta]42 levels were also used to link microsatellite genetic markers to a putative AD genetic locus on chromosome 10 and were observed in patients with incipient sporadic AD. METHODS: The authors measured plasma A[beta]40 and A[beta]42 levels using a sandwich ELISA after the initial examination of 530 individuals participating in an epidemiologic study of aging and dementia. Participants were examined at 18-month intervals, and plasma A[beta]40 and A[beta]42 levels were repeated in 307 subjects 3 years after baseline. RESULTS: Compared with individuals who never developed AD, patients with AD at baseline and those who developed AD during the follow-up had significantly higher A[beta]42, but not A[beta]40, plasma levels. The risk of AD in the highest quartile of plasma A[beta]42 was increased by more than twofold over that in the lowest quartile. The highest plasma A[beta]42 levels were observed in patients with AD who died during the follow-up. Plasma A[beta]42, but not A[beta]40, levels decreased over time in patients with newly acquired AD. CONCLUSIONS: Plasma A[beta]40 and A[beta]42 increase with age and are strongly correlated with each other. Plasma A[beta]40 and A[beta]42 levels are elevated in some patients before and during the early stages of AD but decline thereafter. High plasma A[beta]42 levels may also be associated with mortality in patients with AD.
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The present Elecsys assays produced among the best accuracies and are the first fully automated assays to have these greater accuracies.
“Although previous studies have found associations between CSF and PET Aβ and plasma Aβ using different immunoassays,7,12,13,14,44,45 the present Elecsys assays produced among the best accuracies and they are the first fully automated assays to have these greater accuracies.”
From Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status (2019) · cites this paper as [45]
The improvements in both clinical outcomes are interpreted as evidence of practice effects.
“we interpret this finding as evidence of practice effects, which are increasingly recognized in AMCI[90], are inversely related with conversion to AD, and can be examined as an outcome in clinical trials [91].”
From Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial (2016) · cites this paper as [91]
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- Authors
- Mayeux, R., Honig, L. S., Tang, M.-X., Manly, J., Stern, Y., Schupf, N., & Mehta, P. D.
- Affiliations
- Columbia University Irving Medical Center (US)
- Venue
- Neurology
- Published
- 2003-11-11
- Volume
- 61
- Issue
- 9
- Pages
- 1185-1190
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2065184319
- Cited by
- 434
- References
- 45
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 12 · 2023: 10 · 2022: 6 · 2021: 17 · 2020: 16 · 2019: 13 · 2018: 11 · 2017: 19 · 2016: 18 · 2015: 24 · 2014: 23 · 2013: 19 · 2012: 29
- FWCI
- 10.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG08702, P01AG007232, AG 07232, P50AG008702)
- 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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, Aβ40, amyloid-beta 42, plasma biomarkers, early-onset familial Alzheimer's disease, sporadic Alzheimer's disease, dementia risk, disease progression, mortality, aging
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Female, Follow-Up Studies, Humans, Lipids, Male, Neuropsychological Tests, New York City, Peptide Fragments, Predictive Value of Tests, Body Mass Index, Multivariate Analysis, Proportional Hazards Models, Amyloid beta-Peptides, Age Distribution, Risk Assessment
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