Amyloid probability in Alzheimer disease from plasma, cerebrospinal fluid, and amyloid imaging

Abstract Blood-based biomarkers are increasingly used to triage patients for amyloid confirmation, yet performance is often reported versus a single comparator despite discordance between amyloid PET and CSF. In a cross-sectional secondary analysis of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we assembled one PET-anchored PET–CSF–plasma triad per participant ( n = 320). Bayesian latent class models integrating PET, CSF and plasma (Aβ42/40 or %p-tau217) estimated pattern-level posterior probabilities of latent amyloid positivity, with prespecified sensitivity analyses for PET–CSF conditional dependence, timing gaps (≤7, 8–30, >30 days) and CSF cutpoints. Concordant PET + /CSF+ and PET − /CSF− patterns mapped to probabilities near 1 and 0, whereas discordant patterns yielded intermediate probabilities refined by plasma strata and most sensitive to dependence assumptions. PET–CSF discordance occurred even within ≤7 days (12/98; 12%). A CSF Aβ42 coverage analysis showed similar gradients. Pattern-to-probability reporting may aid interpretation without privileging a reference test.

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Publication Details

Journal
npj Dementia
Published
2026-07-01
DOI
https://doi.org/10.1038/s44400-026-00109-4
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Amyloid probability in Alzheimer disease from plasma, cerebrospinal fluid, and amyloid imaging

Satwant Kumar, Khushboo Verma
npj Dementia
Dementia and Cognitive Impairment Research
article

Amyloid probability in Alzheimer disease from plasma, cerebrospinal fluid, and amyloid imaging

Satwant Kumar, Khushboo Verma
article en

Abstract

Abstract Blood-based biomarkers are increasingly used to triage patients for amyloid confirmation, yet performance is often reported versus a single comparator despite discordance between amyloid PET and CSF. In a cross-sectional secondary analysis of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we assembled one PET-anchored PET–CSF–plasma triad per participant ( n = 320). Bayesian latent class models integrating PET, CSF and plasma (Aβ42/40 or %p-tau217) estimated pattern-level posterior probabilities of latent amyloid positivity, with prespecified sensitivity analyses for PET–CSF conditional dependence, timing gaps (≤7, 8–30, >30 days) and CSF cutpoints. Concordant PET + /CSF+ and PET − /CSF− patterns mapped to probabilities near 1 and 0, whereas discordant patterns yielded intermediate probabilities refined by plasma strata and most sensitive to dependence assumptions. PET–CSF discordance occurred even within ≤7 days (12/98; 12%). A CSF Aβ42 coverage analysis showed similar gradients. Pattern-to-probability reporting may aid interpretation without privileging a reference test.

npj DementiaVol. 2(1)
The University of Texas at Tyler (US), United Way of Smith County (US)
U.S. Department of Defense, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, University of Southern California, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, Eisai, Servier, H. Lundbeck A/S, IXICO, National Institutes of Health, Genentech, Canadian Institutes of Health Research
Openalex Percentile: Top 7%
Dementia and Cognitive Impairment Research
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