Plasma p-tau231 and p-tau217 inform on tau tangles aggregation in cognitively impaired individuals

Abstract

Introduction: Phosphorylated tau (p-tau) biomarkers have been recently proposed to represent brain amyloid-β (Aβ) pathology. Here, we evaluated the plasma biomarkers' contribution beyond the information provided by demographics (age and sex) to identify Aβ and tau pathologies in individuals segregated as cognitively unimpaired (CU) and impaired (CI).

Methods: We assessed 138 CU and 87 CI with available plasma p-tau231, 217⁺ , and 181, Aβ42/40, GFAP and Aβ- and tau-PET.

Results: In CU, only plasma p-tau231 and p-tau217⁺ significantly improved the performance of the demographics in detecting Aβ-PET positivity, while no plasma biomarker provided additional information to identify tau-PET positivity. In CI, p-tau217⁺ and GFAP significantly contributed to demographics to identify both Aβ-PET and tau-PET positivity, while p-tau231 only provided additional information to identify tau-PET positivity.

Discussion: Our results support plasma p-tau231 and p-tau217⁺ as state markers of early Aβ deposition, but in later disease stages they inform on tau tangle accumulation.

Highlights: It is still unclear how much plasma biomarkers contribute to identification of AD pathology across the AD spectrum beyond the information already provided by demographics (age + sex). Plasma p-tau231 and p-tau217⁺ contribute to demographic information to identify brain Aβ pathology in preclinical AD. In CI individuals, plasma p-tau231 contributes to age and sex to inform on the accumulation of tau tangles, while p-tau217⁺ and GFAP inform on both Aβ deposition and tau pathology.

Keywords: PET; demographics; p-tau; plasma biomarkers; tau pathology.