TY - JOUR
T1 - Plasma phosphorylated-tau181 as a predictive biomarker for Alzheimer’s amyloid, tau and FDG PET status
AU - Alzheimer’s Disease Neuroimaging Initiative
AU - Shen, Xue Ning
AU - Huang, Yu Yuan
AU - Chen, Shi Dong
AU - Guo, Yu
AU - Tan, Lan
AU - Dong, Qiang
AU - Yu, Jin Tai
AU - Weiner, Michael W.
AU - Aisen, Paul
AU - Petersen, Ronald
AU - Jack, Clifford R.
AU - Jagust, William
AU - Trojanowki, John Q.
AU - Toga, Arthur W.
AU - Beckett, Laurel
AU - Green, Robert C.
AU - Saykin, Andrew J.
AU - Morris, John C.
AU - Perrin, Richard J.
AU - Shaw, Leslie M.
AU - Carrillo, Maria
AU - Potter, William
AU - Barnes, Lisa
AU - Bernard, Marie
AU - González, Hector
AU - Ho, Carole
AU - Hsiao, John K.
AU - Jackson, Jonathan
AU - Masliah, Eliezer
AU - Masterman, Donna
AU - Okonkwo, Ozioma
AU - Ryan, Laurie
AU - Silverberg, Nina
AU - Fleisher, Adam
AU - Fockler, Juliet
AU - Conti, Cat
AU - Veitch, Dallas
AU - Neuhaus, John
AU - Jin, Chengshi
AU - Nosheny, Rachel
AU - Ashford, Miriam
AU - Flenniken, Derek
AU - Kormos, Adrienne
AU - Jimenez, Gustavo
AU - Donohue, Michael
AU - Gessert, Devon
AU - Salazar, Jennifer
AU - Zimmerman, Caileigh
AU - Grossman, Hillel
AU - Goldstein, Martin A.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85119456383&partnerID=8YFLogxK
U2 - 10.1038/s41398-021-01709-9
DO - 10.1038/s41398-021-01709-9
M3 - Article
C2 - 34775468
AN - SCOPUS:85119456383
SN - 2158-3188
VL - 11
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 585
ER -