The journal of prevention of Alzheimer's disease · 2025
Plasma p-tau217 predicting brain-wide tau accumulation in preclinical AD.
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Moon Hasom, Chen Xi, Alzheimer’s Disease Neuroimaging Initiative
Аннотация
BACKGROUND: Recently developed blood test of Alzheimer's disease (AD) has been recognized as a promising alternative to CSF and PET, as it is noninvasive, cost-effective, and more accessible. Particularly, plasma p-tau217 shows high sensitivity in detecting β-amyloid (Aβ) and tau positivity in early AD. However, the potential value of p-tau217 in revealing Aβ and tau distribution and predicting future development has not been studied.
OBJECTIVES: We investigated the dose-response associations between p-tau217 and regional Aβ and tau measured by PET, as well as the longitudinal prediction of p-tau217 for prospective Aβ and tau accumulation measured by longitudinal PET.
DESIGN: Cross-sectional and longitudinal analyses.
SETTING: We used data in Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) study (N = 333) for primary analyses and Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 410) for validation.
PARTICIPANTS: Cognitively unimpaired older adults (N = 333) from A4 study and cognitively unimpaired older adults (N = 222), mild cognitive impairment (N = 114), and dementia (N = 74) from ADNI.
MEASUREMENTS: Plasma p-tau217 was measured using Lilly (A4) and Fujirebio (ADNI) assays. 18-FFlorbetapir PET and 18-FFlortaucipir PET measured regional Aβ and tau.
RESULTS: Plasma p-tau217 was associated with concurrent Aβ in most cortical regions and tau in temporo-parietal cortices. Longitudinally, p-tau217 predicted brain-wide tau accumulation in widespread cortical regions in preclinical AD, but not Aβ change anywhere.
CONCLUSIONS: Plasma p-tau217 shows dose-response, brain-wide relationships with concurrent Aβ and future tau development in preclinical AD, suggesting its potential in disease trajectory monitoring and large-scale screening for individuals approaching certain biological stages of AD in clinical trials.
OBJECTIVES: We investigated the dose-response associations between p-tau217 and regional Aβ and tau measured by PET, as well as the longitudinal prediction of p-tau217 for prospective Aβ and tau accumulation measured by longitudinal PET.
DESIGN: Cross-sectional and longitudinal analyses.
SETTING: We used data in Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) study (N = 333) for primary analyses and Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 410) for validation.
PARTICIPANTS: Cognitively unimpaired older adults (N = 333) from A4 study and cognitively unimpaired older adults (N = 222), mild cognitive impairment (N = 114), and dementia (N = 74) from ADNI.
MEASUREMENTS: Plasma p-tau217 was measured using Lilly (A4) and Fujirebio (ADNI) assays. 18-FFlorbetapir PET and 18-FFlortaucipir PET measured regional Aβ and tau.
RESULTS: Plasma p-tau217 was associated with concurrent Aβ in most cortical regions and tau in temporo-parietal cortices. Longitudinally, p-tau217 predicted brain-wide tau accumulation in widespread cortical regions in preclinical AD, but not Aβ change anywhere.
CONCLUSIONS: Plasma p-tau217 shows dose-response, brain-wide relationships with concurrent Aβ and future tau development in preclinical AD, suggesting its potential in disease trajectory monitoring and large-scale screening for individuals approaching certain biological stages of AD in clinical trials.