ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
AD-related plasma biomarkers in centenarians: links to cognition and neuropathology.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Advancing a systems-level understanding of neurodegeneration: the BrightFocus Alzheimer's disease research portfolio.Molecular neurodegeneration · 2026Article
- AD-related plasma biomarkers in centenarians: links to cognition and neuropathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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14 authors.
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Abstract
introductionWhether Alzheimer's disease (AD)-associated plasma biomarkers reflect cognitive performance and neuropathology in the oldest old remains unclear.
methodsIn plasma samples from 255 centenarians from the longitudinal 100-plus Study (median age 101.2 years), we quantified biomarkers amyloid beta (Aβ)42/40 ratio, Aβ40, Aβ42, phosphorylated tau 181 (pTau-181)/Aβ42 ratio, pTau-181, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) concentrations. These were associated with same-day measures of cognitive performance and, for centenarians who donated their brain (n = 60), with post mortem Aβ and tau neuropathology.
resultsCognition ranged from high to early cognitive decline (median Mini-Mental State Examination [MMSE] score = 26). Lower plasma Aβ40 and Aβ42 are associated with poorer executive functioning, attention/processing speed, and higher Aβ neuropathology. Elevated plasma NfL and GFAP are associated with poorer executive functioning, slower processing speed, and Aβ and tau neuropathology. Higher plasma pTau-181 and the pTau-181/Aβ42 ratio are associated with Aβ and tau neuropathology, but not with cognitive performance. The Aβ42/40 ratio was uninformative. DISCUSSION: Plasma Aβ, NfL, and GFAP detected neuropathology and early cognitive decline in centenarians; plasma pTau-181 and the pTau-181/Aβ42 ratio primarily report more advanced neuropathology. HIGHLIGHTS: Lower plasma Aβ40 and Aβ42 concentrations are associated with poorer executive functioning and higher Aβ neuropathology, and thus may detect early cognitive decline in centenarians. Higher plasma pTau-181 concentrations and the pTau-181/Aβ42 ratio are strongly associated with Aβ and tau neuropathology; however, they are not associated with cognitive performance. Higher NfL concentrations are associated with higher Aβ and tau neuropathology. Higher plasma NfL and GFAP concentrations are associated with poorer attention and processing speed and may detect early cognitive decline in centenarians.
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