ArticleAnnals of neurology2025
Timing of Changes in Alzheimer's Disease Plasma Biomarkers as Assessed by Amyloid and Tau PET Clocks.
Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Do amyloid trajectories reach a ceiling? Evidence from iterative approximation and simulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Exploring longitudinal relationships among Alzheimer's disease biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Biomarker Variability Limits Individualized Amyloid Time Estimation in Alzheimer Disease.bioRxiv : the preprint server for biology · 2026Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Exploring the Gut-Brain Connection: Are Probiotics the Next Frontier in Alzheimer's Disease Treatment?Probiotics and antimicrobial proteins · 2026Review
- Plasma p-Tau217 and Aβ42/Aβ40 mediate the association between minimal depressive symptoms and cognitive impairment.Journal of neurology · 2026Article
- Multi-domain AD risk burden and plasma biomarkers in cognitively unimpaired adults.medRxiv : the preprint server for health sciences · 2026Article
- Estimating the time course of biomarker changes in Alzheimer's disease.Brain : a journal of neurology · 2026Article
- Brain, benefit, or burden? Revisiting statins and cognitive function in older adults.GeroScience · 2026Review
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Comparative analyses of Alzheimer's disease blood biomarkers and cognitive domains.medRxiv : the preprint server for health sciences · 2026Article
- Plasma biomarker trajectories across Alzheimer's clinical onset: a 17-year prospective study.Alzheimer's research & therapy · 2026Article
- Trajectories of plasma and CSF MTBR-tau243 and phosphorylated-tau species across the Alzheimer's disease continuum.Nature communications · 2026Article
- Blood-based biomarkers of Alzheimer's disease: potential utility in clinical practice.Current opinion in neurology · 2026Review
- Presymptomatic plasma biomarkers in autosomal dominant Alzheimer's disease: sequence and timing.medRxiv : the preprint server for health sciences · 2026Article
- Ancestry-specific effects ofmedRxiv : the preprint server for health sciences · 2026Article
- PET Imaging in Alzheimer Disease in the Era of Antiamyloid Therapy in the United States: Clinical Utility, Quantification, and Policy Landscape.Journal of nuclear medicine technology · 2026Review
- Predicting onset of symptomatic Alzheimer's disease with plasma p-tau217 clocks.Nature medicine · 2026Article
- Postmortem Associations Between Alzheimer Disease Pathology and Plasma pTau217, GFAP, and NfL in AD and AD-Related Dementias.Neurology · 2026Article
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Abstract
objectiveThe objective of this study was to evaluate the timing of change of Alzheimer's disease (AD) plasma biomarkers (Aβ42/Aβ40, p-tau217, p-tau181, GFAP, and NfL) from six different assay platforms, alongside established AD biomarkers, using amyloid and tau positron emission tomography (PET)-based AD progression timelines.
methodsData from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 784 individuals with longitudinal amyloid PET and 359 with longitudinal tau PET, were analyzed to estimate the age at amyloid and tau PET positivity, respectively. Longitudinal plasma biomarker measurements were available from 190 individuals with an estimated amyloid PET positivity age and from 70 individuals with an estimated tau PET positivity age. In a subset of 17 clinical progressors, age at tau PET positivity strongly predicted symptom onset, allowing for estimation of symptom onset age. Biomarker trajectories based on time from amyloid or tau PET positivity or symptom onset were modelled using Generalized Additive Mixed models. Time intervals of significant biomarker change and the earliest timepoints at which biomarkers exceeded predefined abnormality thresholds were identified.
resultsAll plasma biomarkers except NfL became abnormal prior to established thresholds for amyloid and tau PET positivity. Plasma Aβ42/Aβ40 became abnormal very early in both amyloid PET and tau PET timelines, while plasma GFAP became abnormal early in the tau PET timeline. Plasma Aβ42/Aβ40 levels plateaued, whereas plasma p-tau217, p-tau181, GFAP, and NfL levels increased throughout the modeled disease progression. Some variations in the timing of these changes were observed across different biomarker assays.
interpretationThese findings suggest that the plasma Aβ42/Aβ40 may be useful in identifying individuals with very low levels of amyloid pathology, whereas p-tau, GFAP, and NfL may be useful in staging disease progression. ANN NEUROL 2025;98:508-523.
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