Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads

Autor: Gemma Salvadó, Rik Ossenkoppele, Nicholas J Ashton, Thomas G Beach, Geidy E Serrano, Eric M Reiman, Henrik Zetterberg, Niklas Mattsson‐Carlgren, Shorena Janelidze, Kaj Blennow, Oskar Hansson
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 15, Iss 5, Pp 1-16 (2023)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.202217123
Popis: Abstract Several promising plasma biomarkers for Alzheimer's disease have been recently developed, but their neuropathological correlates have not yet been fully determined. To investigate and compare independent associations between multiple plasma biomarkers (p‐tau181, p‐tau217, p‐tau231, Aβ42/40, GFAP, and NfL) and neuropathologic measures of amyloid and tau, we included 105 participants from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with antemortem plasma samples and a postmortem neuropathological exam, 48 of whom had longitudinal p‐tau217 and p‐tau181. When simultaneously including plaque and tangle loads, the Aβ42/40 ratio and p‐tau231 were only associated with plaques (ρAβ42/40[95%CI] = −0.53[−0.65, −0.35], ρp‐tau231[95%CI] = 0.28[0.10, 0.43]), GFAP was only associated with tangles (ρGFAP[95%CI] = 0.39[0.17, 0.57]), and p‐tau217 and p‐tau181 were associated with both plaques (ρp‐tau217[95%CI] = 0.40[0.21, 0.56], ρp‐tau181[95%CI] = 0.36[0.15, 0.50]) and tangles (ρp‐tau217[95%CI] = 0.52[0.34, 0.66]; ρp‐tau181[95%CI] = 0.36[0.17, 0.52]). A model combining p‐tau217 and the Aβ42/40 ratio showed the highest accuracy for predicting the presence of Alzheimer's disease neuropathological change (ADNC, AUC[95%CI] = 0.89[0.82, 0.96]) and plaque load (R2 = 0.55), while p‐tau217 alone was optimal for predicting tangle load (R2 = 0.45). Our results suggest that high‐performing assays of plasma p‐tau217 and Aβ42/40 might be an optimal combination to assess Alzheimer's‐related pathology in vivo.
Databáze: Directory of Open Access Journals
Externí odkaz: