Plasma P-tau181 and P-tau217 in Patients With Traumatic Encephalopathy Syndrome With and Without Evidence of Alzheimer Disease Pathology.

Autor:	Asken BM; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco. breton.asken@ucsf.edu., Tanner JA; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., VandeVrede L; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Mantyh WG; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Casaletto KB; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Staffaroni AM; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., La Joie R; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Iaccarino L; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Soleimani-Meigooni D; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Rojas JC; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Gardner RC; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Miller BL; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Grinberg LT; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Boxer AL; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Kramer JH; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco., Rabinovici GD; From the Memory and Aging Center (B.M.A.T.C., J.A.T., L.V., W.G.M., K.B.C., A.M.S., R.L.J., L.I., D.S.-M., J.C.R., R.C.G., B.L.M., L.T.G., A.L.B., J.H.K., G.D.R.), Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (W.G.M.), University of Minnesota, Minneapolis; San Francisco Veterans Affairs Medical Center (R.C.G.); and Department of Radiology & Biomedical Imaging, University of California (G.D.R.), San Francisco.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2022 Aug 09; Vol. 99 (6), pp. e594-e604. Date of Electronic Publication: 2022 May 16.
DOI:	10.1212/WNL.0000000000200678
Abstrakt:	Background and Objectives: Traumatic encephalopathy syndrome (TES) has overlapping clinical symptoms with Alzheimer disease (AD). AD pathology commonly co-occurs with chronic traumatic encephalopathy (CTE) pathology. There are currently no validated CTE biomarkers. AD-specific biomarkers such as plasma P-tau181 and P-tau217 may help to identify patients with TES who have AD pathology. Methods: We measured plasma P-tau181 and P-tau217 (Meso Scale Discovery electrochemiluminescence) in patients with TES, mild cognitive impairment/dementia with biomarker-confirmed AD ("AD"), and healthy controls ("HC"). Patients underwent amyloid-beta (Aβ)-PET and a subset underwent tau-PET using [18F]Flortaucipir. We compared plasma P-tau levels controlling for age and sex and also performed AUC analyses to evaluate the accuracy of group differentiation. In patients with TES, we evaluated associations between plasma P-tau, years of repetitive head impact exposure, and tau-PET. Four TES patients with autopsy-confirmed CTE were described qualitatively. Results: The sample included 131 participants (TES, N = 18; AD, N = 65; HC, N = 48). Aβ(+) patients with TES (N = 10), but not Aβ(-) TES, had significantly higher plasma P-tau levels than HC (P-tau181: p < 0.001, d = 1.34; P-tau217: p < 0.001, d = 1.59). There was a trend for Aβ(+) TES having higher plasma P-tau than Aβ(-) TES (P-tau181: p = 0.06, d = 1.06; P-tau217: p = 0.09, d = 0.93). AUC analyses showed good classification of Aβ(+) TES from HC for P-tau181 (AUC = 0.87 [0.71-1.00]) and P-tau217 (AUC = 0.93 [0.86-1.00]). Plasma P-tau217 showed fair differentiation of Aβ(+) TES from Aβ(-) TES (AUC = 0.79 [0.54-1.00], p = 0.04), whereas classification accuracy of P-tau181 was slightly lower and not statistically significant (AUC = 0.71 [0.46-0.96], p = 0.13). Patients with AD had higher tau-PET tracer uptake than Aβ(+) TES and were well differentiated using P-tau181 (AUC = 0.81 [0.68-0.94]) and P-tau217 (AUC = 0.86 [0.73-0.98]). Plasma P-tau correlated with the tau-PET signal in Aβ(+) TES but not in Aβ(-) TES, and there was no association between plasma P-tau and years of repetitive head impact exposure. TES patients with severe CTE and no AD at autopsy had low P-tau181 and P-tau217 levels. Discussion: Measuring P-tau181 and P-tau217 in plasma may be a feasible and scalable fluid biomarker for identifying AD pathology in TES. Low plasma P-tau levels may be used to increase clinical suspicion of CTE over AD as a primary pathology in TES. Currently, there is no support for P-tau181 or P-tau217 as in vivo biomarkers of CTE tau. Larger studies of patients with pathologically confirmed CTE are needed. Classification of Evidence: This study provides Class III evidence that (1) among patients with TES and abnormal Aβ-PET scans, elevated plasma P-tau can differentiate between affected individuals and HCs; (2) low plasma P-tau may help identify patients with TES who do not have Alzheimer; and (3) plasma P-tau181 and P-tau217 are not useful biomarkers of patients with TES who do not have AD. (© 2022 American Academy of Neurology.)
Databáze:	MEDLINE
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