Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease
Open accessAbstract
Plasma Aβ42 and Aβ40 levels are putative biomarkers for Alzheimer's disease (AD), but their significance and predictive value have been inconclusive. In AD transgenic models, plasma and cerebrospinal fluid levels of Aβ42 and Aβ40 increase with age but subsequently decrease when Aβ begins to accumulate in brain and with the onset of cognitive impairment. To determine the predictive value of Aβ levels in elderly populations, we investigated how plasma Aβ42, Aβ40, and a protofibrillar subspecies of Aβ42 changed over time and with the onset of cognitive impairment or AD. In a cohort of 1,125 elderly persons without dementia, 104 (9.2%) of the participants developed AD over 4.6 years of follow-up. Higher plasma Aβ42 levels at the onset of the study were associated with a threefold increased risk of AD. However, conversion to AD was accompanied by a significant decline in plasma Aβ42, a decreased Aβ42/Aβ40 ratio and, with the onset of cognitive impairment, decreased protofibrillar Aβ42 levels. Our results suggest individuals with elevated plasma Aβ42 are at increased risk of AD and that with the onset of disease, the decline in some forms of Aβ may reflect compartmentalization of Aβ peptides in the brain.
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In elderly people, those with increased Aβ42 levels over the follow-up period were three times more likely to develop AD compared with those with decreasing levels.
“Monitoring the levels, it was seen that those with increased Aβ42 levels over the follow-up period, compared with decreasing levels were three times more likely to develop AD [59].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [59]
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- Authors
- Schupf, N., Tang, M. X., Fukuyama, H., Manly, J., Andrews, H., Mehta, P., Ravetch, J., & Mayeux, R.
- Affiliations
- *Taub Institute for Research on Alzheimer's Disease and the Aging Brain,
- Columbia University (US)
- Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY 10065
- Department of Immunology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314; and
- Rockefeller University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-09-16
- Volume
- 105
- Issue
- 37
- Pages
- 14052-14057
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2544577
- OpenAlex
- W2050607653
- Cited by
- 225
- References
- 53
- Citations by year
- 2025: 5 · 2024: 3 · 2023: 9 · 2022: 5 · 2021: 5 · 2020: 13 · 2019: 8 · 2018: 11 · 2017: 9 · 2016: 14 · 2015: 16 · 2014: 19 · 2013: 21 · 2012: 26
- FWCI
- 13.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P01AG007232, P50AG008702, P01AG07232, P50AG08702)
- 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, amyloid-beta, amyloid-beta 42, Aβ40, plasma biomarkers, risk biomarkers, cognitive impairment, disease transformation, Aβ42/Aβ40 ratio, transgenic mouse model
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Risk Factors, Biomarkers, Amyloid beta-Peptides
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