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Antemortem plasma phosphorylated tau (181) predicts Alzheimer’s disease neuropathology and regional tau at autopsy



Morrison, Madeline S;

Aparicio, Hugo J;

Blennow, Kaj;

Zetterberg, Henrik;

Ashton, Nicholas J;

Karikari, Thomas K;

Tripodis, Yorghos;

Alosco, Michael L; + view all

Morrison, Madeline S;

Aparicio, Hugo J;

Blennow, Kaj;

Zetterberg, Henrik;

Ashton, Nicholas J;

Karikari, Thomas K;

Tripodis, Yorghos;

Martin, Brett;

Palmisano, Joseph N;

Sugarman, Michael A;

Frank, Brandon;

Steinberg, Eric G;

Turk, Katherine W;

Budson, Andrew E;

Au, Rhoda;

Goldstein, Lee E;

Jun, Gyungah R;

Kowall, Neil W;

Killiany, Ronald;

Qiu, Wei Qiao;

Stern, Robert A;

Mez, Jesse;

McKee, Ann C;

Stein, Thor D;

Alosco, Michael L;

– view fewer

(2022)

Antemortem plasma phosphorylated tau (181) predicts Alzheimer’s disease neuropathology and regional tau at autopsy.

Brain


10.1093/brain/awac175.

(In press).


Text

awac175.pdf
– Accepted Version

Access restricted to UCL open access staff until 17 November 2022.

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Abstract

Blood-based biomarkers such as tau phosphorylated at threonine 181 (phosphorylated-tau181) represent an accessible, cost-effective, and scalable approach for the in vivo detection of Alzheimer’s disease pathophysiology. Plasma-pathological correlation studies are needed to validate plasma phosphorylated-tau181 as an accurate and reliable biomarker of Alzheimer’s disease neuropathologic changes. This plasma-to-autopsy correlation study included participants from the Boston University Alzheimer’s Disease Research Center who had a plasma sample analyzed for phosphorylated-tau181 between 2008-2018 and donated their brain for neuropathological examination. Plasma phosphorelated-tau181 was measured with single molecule array technology. Of 103 participants, 62 (60.2%) had autopsy-confirmed Alzheimer’s disease. Average time between blood draw and death was 5.6 years (SD = 3.1 years). Multivariable analyses showed higher plasma phosphorylated-tau181 concentrations were associated with increased odds for having autopsy-confirmed Alzheimer’s disease (AUC = 0.82, OR = 1.07, 95% CI = 1.03-1.11, p < 0.01; phosphorylated-tau standardized [z-transformed]: OR = 2.98, 95% CI = 1.50-5.93, p < 0.01). Higher plasma phosphorylated-tau181 levels were associated with increased odds for having a higher Braak stage (OR = 1.06, 95% CI = 1.02-1.09, p < 0.001) and more severe phosphorylated-tau across six cortical and subcortical brain regions (ORs = 1.03-1.06, p < 0.05). The association between plasma phosphorylated-tau181 and Alzheimer’s disease was strongest in those who were demented at time of blood draw (OR = 1.25, 95%CI = 1.02-1.53), but an effect existed among the non-demented (OR = 1.05, 95% CI = 1.01-1.10). There was higher discrimination accuracy for Alzheimer’s disease when blood draw occurred in years closer to death, however, higher plasma phosphorylated-tau181 levels were associated with Alzheimer’s disease even when blood draw occurred >5 years from death. Antemortem plasma phosphorylated-tau181 concentrations were associated with Alzheimer’s disease neuropathology and accurately differentiated brain donors with and without autopsy-confirmed Alzheimer’s disease. These findings support plasma phosphorylated-tau181 as a scalable biomarker for the detection of Alzheimer’s disease.

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