Plasma P-tau181 and P-tau217 in Patients With Traumatic Encephalopathy Syndrome With and Without Evidence of Alzheimer Disease Pathology.
|
| Abstract | 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.
|
|---|---|
| Authors | Breton M Asken, Jeremy A Tanner, Lawren VandeVrede, William G Mantyh, Kaitlin B Casaletto, Adam M Staffaroni, Renaud La Joie, Leonardo Iaccarino, David Soleimani-Meigooni, Julio C Rojas, Raquel C Gardner, Bruce L Miller, Lea T Grinberg, Adam L Boxer, Joel H Kramer, Gil D Rabinovici |
| Journal | Neurology (Neurology) Vol. 99 Issue 6 Pg. e594-e604 (08 09 2022) ISSN: 1526-632X [Electronic] United States |
| PMID | 35577574 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural) |
| Copyright | © 2022 American Academy of Neurology. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!