@article{a6aa8736f7ee45e395d594c959dfd278,
title = "Tau phosphorylation sites serine202 and serine396 are differently altered in chronic traumatic encephalopathy and Alzheimer's disease",
abstract = "Introduction: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI) typically sustained by contact sport athletes. Post-translation modifications to tau in CTE have not been well delineated or compared to Alzheimer's disease (AD). Methods: We measured phosphorylated tau epitopes within dorsolateral frontal cortex from post mortem brains with neither CTE nor AD (n = 108), CTE (n = 109), AD (n = 223), and both CTE and AD (n = 33). Results: Levels of hyperphosphorylated tau (p-tau)202, p-tau231, and p-tau396 were significantly increased in CTE. Total years of RHI exposure was significantly associated with increased p-tau202 levels (P =.001), but not p-tau396. Instead, p-tau396 was most closely related to amyloid beta (Aβ)1-42 levels (P <.001). The p-tau202:p-tau396 ratio was significantly increased in early and late CTE compared to AD. Discussion: In frontal cortex, p-tau202 is the most upregulated p-tau species in CTE, while p-tau396 is most increased in AD. p-tau202 and p-tau396 measurements may aid in developing biomarkers for disease.",
keywords = "Alzheimer's disease, amyloid beta peptides, brain, chronic traumatic encephalopathy, football, humans, male, microtubule-associated proteins, pathology, statistics and numerical data, tau proteins, tauopathies",
author = "Stathas, {Spiro Anthony} and Alvarez, {Victor E.} and Weiming Xia and Raymond Nicks and Gaoyuan Meng and Sarah Daley and Morgan Pothast and Arsal Shah and Hunter Kelley and Camille Esnault and Robert McCormack and Erin Dixon and Lucas Fishbein and Cherry, {Jonathan D.} and Huber, {Bertrand R.} and Yorghos Tripodis and Alosco, {Michael L.} and Jesse Mez and McKee, {Ann C.} and Stein, {Thor D.}",
note = "Funding Information: This work was supported by the United States (U.S.) Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award (I01-CX001038); Alzheimer's Association (NIRG-305779, NIRG-362697); National Institute of Aging (RF1AG054156, R56AG057768, RF1AG057768, K23AG046377, U19AG068753, AG08122, AG054076); National Institute of Neurological Disorders and Stroke (U54NS115266, U01NS086659, K23NS102399); National Institute of Aging Boston University AD Center (P30AG13846; supplement 0572063345-5; P30AG072978); National Heart, Lung and Blood Institute (75N92019D00031 and HHSN2682015000011); Department of Defense Peer Reviewed Alzheimer's Research Program (PRARP #13267017); and the Concussion Legacy Foundation. This work was also supported by unrestricted gifts from the Andlinger Foundation and WWE. We gratefully acknowledge the use of resources and facilities at the Edith Nourse Rogers Memorial Veterans Hospital (Bedford, MA) as well as all the individuals whose participation and contributions made this work possible. Funding Information: This work was supported by the United States (U.S.) Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award (I01‐CX001038); Alzheimer's Association (NIRG‐305779, NIRG‐362697); National Institute of Aging (RF1AG054156, R56AG057768, RF1AG057768, K23AG046377, U19AG068753, AG08122, AG054076); National Institute of Neurological Disorders and Stroke (U54NS115266, U01NS086659, K23NS102399); National Institute of Aging Boston University AD Center (P30AG13846; supplement 0572063345‐5; P30AG072978); National Heart, Lung and Blood Institute (75N92019D00031 and HHSN2682015000011); Department of Defense Peer Reviewed Alzheimer's Research Program (PRARP #13267017); and the Concussion Legacy Foundation. This work was also supported by unrestricted gifts from the Andlinger Foundation and WWE. We gratefully acknowledge the use of resources and facilities at the Edith Nourse Rogers Memorial Veterans Hospital (Bedford, MA) as well as all the individuals whose participation and contributions made this work possible. Funding Information: Outside of the submitted work, WX received research support from the National Institutes of Health, Veterans Health Administration, Biomedical Laboratory Research and Development, and Veterans Health Administration, Clinical Sciences Research and Development Merit Awards. He reports being principal investigator and co‐investigator on clinical trials, and has a patent pending regarding the diagnosis of AD using machine learning. JDC received grant support from the Department of Veterans Affairs Career Development Award and National Institute of Aging Boston University AD Center. YT reports receiving grant support to the Boston University School of Public Health. MLA has received a grant from the National Institute of Neurological Disorders and Stroke (NINDS); royalties from Oxford University; consulting fees from Corino Therapeutics, Inc.; and honoraria from the International Neuropsychological Society, American Academy of Neurology, and Neuroscience Grand Rounds at Allegheny General Hospital. JM received support for the submitted work from the NIH and DOD and additional grants from the National Institute of Aging (NIA), Department of Defense, and NINDS. ACM reports grant support for other works from the NINDS/NIA, NIA, and VA, and honoraria from the University of Massachusetts, Montefiore Medical Center, Korean Dementia Society, and Texas Neurological Society. The remaining authors report no relevant conflicts of interest. Publisher Copyright: {\textcopyright} 2021 the Alzheimer's Association.",
year = "2022",
month = aug,
doi = "10.1002/alz.12502",
language = "English (US)",
volume = "18",
pages = "1511--1522",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier",
number = "8",
}