Shen, XN; Huang, YY; Chen, SD; Guo, Y; Tan, L; Dong, Q; Yu, JT; ... Shaw, LM; + view all Shen, XN; Huang, YY; Chen, SD; Guo, Y; Tan, L; Dong, Q; Yu, JT; Weiner, MW; Aisen, P; Petersen, R; Jack, CR; Jagust, W; Trojanowki, JQ; Toga, AW; Beckett, L; Green, RC; Saykin, AJ; Morris, JC; Perrin, RJ; Shaw, LM; Carrillo, M; Potter, W; Barnes, L; Bernard, M; González, H; Ho, C; Hsiao, JK; Jackson, J; Masliah, E; Masterman, D; Okonkwo, O; Perrin, R; Ryan, L; Silverberg, N; Fleisher, A; Fockler, J; Conti, C; Veitch, D; Neuhaus, J; Jin, C; Nosheny, R; Ashford, M; Flenniken, D; Kormos, A; Jimenez, G; Donohue, M; Gessert, D; Salazar, J; Zimmerman, C; Cabrera, Y; Walter, S; Miller, G; Coker, G; Clanton, T; Hergesheimer, L; Smith, S; Adegoke, O; Mahboubi, P; Moore, S; Pizzola, J; Shaffer, E; Sloan, B; Harvey, D; Borowski, B; Ward, C; Schwarz, C; Jones, D; Gunter, J; Kantarci, K; Senjem, M; Vemuri, P; Reid, R; Fox, NC; Malone, I; Thompson, P; Thomopoulos, SI; Nir, TM; Jahanshad, N; DeCarli, C; Knaack, A; Fletcher, E; Tosun-Turgut, D; Chen, SR; Choe, M; Crawford, K; Yushkevich, PA; Das, S; Koeppe, RA; Reiman, EM; Chen, K; Mathis, C; Landau, S; Perrin, R; Cairns, NJ; Householder, E; Franklin, E; Bernhardt, H; Taylor-Reinwald, L; Shaw, LM; - view fewer (2021) Plasma phosphorylated-tau181 as a predictive biomarker for Alzheimer’s amyloid, tau and FDG PET status. Translational Psychiatry , 11 , Article 585. 10.1038/s41398-021-01709-9.

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Abstract

Plasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer’s pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = 0.45, P < 0.0001), tau (0.25, P = 0.0003), and FDG PET uptakes (−0.37, P < 0.0001), and increased along the Alzheimer’s continuum. Individually, plasma p-tau181 could detect abnormal amyloid, tau pathologies and hypometabolism in the brain, similar with or even better than clinical indicators. The diagnostic accuracy of plasma p-tau181 elevated significantly when combined with clinical information (AUC = 0.814 for amyloid PET, 0.773 for tau PET, and 0.708 for FDG PET). Relationships of plasma p-tau181 with brain pathologies were partly or entirely mediated by the corresponding CSF biomarkers. Besides, individuals with abnormal plasma p-tau181 level (>18.85 pg/ml) at baseline had a higher risk of pathological progression in brain amyloid (HR: 2.32, 95%CI 1.32–4.08) and FDG PET (3.21, 95%CI 2.06–5.01) status. Plasma p-tau181 may be a sensitive screening test for detecting brain pathologies, and serve as a predictive biomarker for Alzheimer’s pathophysiology.

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