Tau-PET subtype modifies the association between plasma p-tau217 and memory in Alzheimer's disease
- 1University of California, Irvine
Abstract
INTRODUCTIONPlasma p-tau217 is associated with Alzheimers disease pathology and memory performance, but its implications for memory may depend on fibrillar tau topography. We examined whether tau-PET subtype modified the association between plasma p-tau217 and memory.
METHODSWe analyzed 396 amyloid-positive, tau-positive participants spanning cognitively unimpaired, mild cognitive impairment, and dementia stages from six cohorts with tau-PET and plasma p-tau217; 301 had harmonized memory data. Tau-PET subtypes were derived using data-driven disease progression modelling. Primary cross-sectional models tested subtypexp-tau217 interactions for memory, adjusting for age, sex, education, APOE {varepsilon}4 status, and cohort. Secondary and exploratory analyses examined latent global cognition, non-memory measures, and longitudinal cognitive change.
RESULTSThree tau-PET subtypes were retained: limbic-predominant, medial temporal lobe (MTL)-sparing, and posterior-predominant. Cross-sectionally, MTL-sparing participants had lower plasma p-tau217 than the other subtypes. The association between higher plasma p-tau217 and worse memory differed by subtype (interaction p=0.002) and was stronger in MTL-sparing (B=-0.191, p<0.001) than in limbic-predominant (B=-0.07, p=0.002) and posterior-predominant participants (B=-0.07, p<0.001). The interaction remained significant after additional adjustment for diagnostic group (p=0.015). This pattern also persisted after additional adjustment for PET tau burden, amyloid Centiloids, or plasma A{beta}42/40; none of these biomarkers showed comparable subtype modification. Subtype modification was also observed for a global cognitive composite (interaction p=0.004) and subsequent memory decline in an exploratory analysis conditioned on baseline memory (interaction p=0.016).
DISCUSSIONTau-PET subtype modified the p-tau217-memory association, suggesting that the cognitive implications of plasma p-tau217 may vary with tau topography.
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BibTeX
@misc{zheng2026taupet,
title = {{Tau-PET subtype modifies the association between plasma p-tau217 and memory in Alzheimer's disease}},
author = {L. Zheng and E. Ghanbarian and C. Albarran Morillo and K. Younes and C. M. Glover and L. A. Rabin and J. D. Grill and M. Ewers and S. A. Sajjadi and A. Ezzati and the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Health and Aging Brain (HABS-HD) Study Team and the PREVENT-AD Research Group},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.26363629},
url = {https://www.medrxiv.org/content/10.64898/2026.09.25.26363629v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Tau-PET subtype modifies the association between plasma p-tau217 and memory in Alzheimer's disease
AU - L. Zheng
AU - E. Ghanbarian
AU - C. Albarran Morillo
AU - K. Younes
AU - C. M. Glover
AU - L. A. Rabin
AU - J. D. Grill
AU - M. Ewers
AU - S. A. Sajjadi
AU - A. Ezzati
AU - the Alzheimer's Disease Neuroimaging Initiative (ADNI)
AU - the Health and Aging Brain (HABS-HD) Study Team
AU - the PREVENT-AD Research Group
PY - 2026
DA - 2026/09/25
PB - medRxiv
DO - 10.64898/2026.09.25.26363629
UR - https://www.medrxiv.org/content/10.64898/2026.09.25.26363629v1
AB - INTRODUCTIONPlasma p-tau217 is associated with Alzheimers disease pathology and memory performance, but its implications for memory may depend on fibrillar tau topography. We examined whether tau-PET subtype modified the association between plasma p-tau217 and memory. METHODSWe analyzed 396 amyloid-positive, tau-positive participants spanning cognitively unimpaired, mild cognitive impairment, and dementia stages from six cohorts with tau-PET and plasma p-tau217; 301 had harmonized memory data. Tau-PET subtypes were derived using data-driven disease progression modelling. Primary cross-sectional models tested subtypexp-tau217 interactions for memory, adjusting for age, sex, education, APOE {varepsilon}4 status, and cohort. Secondary and exploratory analyses examined latent global cognition, non-memory measures, and longitudinal cognitive change. RESULTSThree tau-PET subtypes were retained: limbic-predominant, medial temporal lobe (MTL)-sparing, and posterior-predominant. Cross-sectionally, MTL-sparing participants had lower plasma p-tau217 than the other subtypes. The association between higher plasma p-tau217 and worse memory differed by subtype (interaction p=0.002) and was stronger in MTL-sparing (B=-0.191, p<0.001) than in limbic-predominant (B=-0.07, p=0.002) and posterior-predominant participants (B=-0.07, p<0.001). The interaction remained significant after additional adjustment for diagnostic group (p=0.015). This pattern also persisted after additional adjustment for PET tau burden, amyloid Centiloids, or plasma A{beta}42/40; none of these biomarkers showed comparable subtype modification. Subtype modification was also observed for a global cognitive composite (interaction p=0.004) and subsequent memory decline in an exploratory analysis conditioned on baseline memory (interaction p=0.016). DISCUSSIONTau-PET subtype modified the p-tau217-memory association, suggesting that the cognitive implications of plasma p-tau217 may vary with tau topography.
ER -