Citations 2
Plasma Phosphorylated Tau 217 in Participants at Risk for Chronic Traumatic Encephalopathy
Miner, A, Zetterberg, Henrik, Blennow, Kaj, Groh, Jenna R., Singh, Alpana, Dieckhoff, Kari, Tripodis, Yorghos, Adler, Charles H., Balcer, Laura J. , Bernick, C L, Peskind, Elaine, Asken, Breton M., Tanner, Jeremy A., Rabinovici, Gil D., Banks, Sarah J., Barr, William B., Wethe, Jennifer V., Cantu, Robert C., Dodick, David W., Mez, Jesse, Palmisano, J, Martin, Brett, Stein, Thor D., McKee, Ann C., Cummings, Jeffrey L., Shenton, Martha E., Reiman, E Bieto, Rc, Stern, Ashton, Nicholas J., Alosco, Michael L., Chen, Kewei, Protas, Hillary, Su, Yi, Boker, Connie, Au, Rhoda, Farrer, Lindsay, Helm, Robert, Kowall, Neil, Mercier, Gustavo, Otis, James, Weller, Jason, Bragg, Tahlia, Simkin, Irene, Trujillo-Rodriguez, Diana, Amerongen, Suzan van , Andino, Alondra, Conneely, Shannon, Diamond, Courtney, Fagle, Tessa, Haller, Olivia, Hunt, Tennyson, Gullotti, Nicole, Kossow, Bailey, Kugelmass, Carrie, Mariani, Megan, Mayville, Brian, McLaughlin, Kathleen, Nanna, Mary, DiPopolo, Marty, Platt, Taylor, Rice, Fiona, Sestak, Madison, McClean, Michael, Annis, Douglas, Chaisson, Christine, Dixon, Diane, Finney, Carolyn, Gallagher, Kerrin, Hartlage, Kaitlin , Lu, Jun, Ojo, E O, Pine, Brittany, Ramachandran, Janani, Baucom, Zachary, Tuz‐Zahra, Fatima , Yhang, Eukyung , Bouix, Sylvain, Fitzsimmons, Jennifer, Lin, Alexander P., Koerte, Inga K., Pasternak, Ofer, Arciniega, Hector , Billah, Tashrif , Bonke, Elena, Breedlove, Katherine M. , Carrington, Holly, Coello, Eduardo , Coleman, Michael J., John, Omar , Jung, Leonard, Liao, Huijun, Loy, Maria, Rizzoni, Elizabeth, Schulz, V. D., Silva, Annelise, Vessey, Brynn, Wiegand, Tim L.T, Miller, Jason, Ritter, Aaron , Sabbagh, Marwan, Cruz, Raelynn de la, Durant, Jan, Golceker, Morgan, Harmon, Nicolette, Kaylegian, Jaeson, Long, Rachelle, Nance, Christine, Sandoval, Priscilla, Staples, Miranda, Clark, Emma F., Serrano, Andrew, Geda, Yonas, Duffy, Amy, Falk, Bryce, Howard, Marci, Montague, Michelle , Osgood, Thomas, Babcock, Debra, Bellgowan, Patrick, GOLDBERG, JUDITH, Joseph, Binu , Kirov, Ivan, Lui, Yvonne, Marmar, Charles, Wisniewski, T R, Al-Kharafi, Alhassan, George, Allan, Hasanaj, Lisena, Martin, Sammie, Riley, Edward, Runge, William, Serrano, Liliana , Iliff, Jeffrey, Li, Gail, Janssen, D, Meabon, James, Piantino, Juan, Schindler, Abigail, Thomas, Ronald, Colasurdo, Elizabeth , Shofer, Jane, Marcus, Daniel S., Gurney, Jenny , Greenwald, Richard, Johnson, Keith A., Singh, Alpana , Singh, Alpana , Miner, Annalise E., Zetterberg, Henrik , Blennow, Kaj , Groh, Jenna R. , Singh, Alpana, Tripodis, Yorghos , Adler, Charles H. , Bernick, Charles , Peskind, Elaine R. , Asken, Breton M. , Rabinovici, Gil D. , Banks, Sarah J. , Barr, William , Wethe, Jennifer V. , Cantu, Robert C. , Dodick, David W. , Mez, Jesse , Stein, Thor D. , McKee, Ann C. , Cummings, Jeffrey L. , Shenton, Martha E. , Reiman, Eric M. , Ashton, Nicholas J. , Alosco, Michael L. , Protas, Hillary , Au, Rhoda, Weller, Jason , Trujillo‐Rodriguez, Diana , Fagle, Tessa, Mariani, Megan, McLaughlin, Kathleen , Pulukuri, Surya Vamsi , Sestak, Madison, McClean, Michael D , Annis, Douglas, Finney, Carolyn, Lu, Jun, Pine, Brittany, Ramachandran, Janani , Baucom, Zachary, Bouix, Sylvain , Koerte, Inga K , Pasternak, Ofer , Bonke, Elena M. , Carrington, Holly , Coleman, Michael J. , Liao, Huijun, Schulz, Vivian, Wiegand, Tim L. T. , II, Robert W. Turner , Marek, Kenneth , Geda, Yonas E. , Howard, Marci, Montague, Michelle, Babcock, Debra, Bellgowan, Patrick S.F. , Kirov, Ivan, George, Allan, Meabon, James S. , Piantino, Juan , Thomas, Ronald G. , Colasurdo, Elizabeth A. , Shofer, Jane, Marcus, Daniel S., Johnson, Keith A.
JAMA Network Open | July 13, 2026 | Volume: 9 | Issue: 7 | Pages: e2622966
10.1001/jamanetworkopen.2026.22966
Importance In vivo biomarkers for detecting neuropathologies from repetitive head impacts (RHI), including chronic traumatic encephalopathy (CTE), are needed. Objective To evaluate the utility of plasma phosphorylated tau 217 (p-tau217), assess its performance as a beta-amyloid (Aβ) biomarker in participants with RHI exposure at risk for CTE, and explore concordance with CTE neuropathology in a postmortem subsample. Design, Setting, and Participants This longitudinal, multicenter, case-control study used data from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of CTE (DIAGNOSE CTE) Research Project, collected from September 2016 to October 2023. Participants were former American football players (case participants) and asymptomatic men unexposed to RHI (control participants). A subsample had available neuropathologic data. Exposures RHI, traumatic encephalopathy syndrome (TES) diagnoses, and levels of CTE certainty. Main Outcomes and Measures Plasma p-tau217 (classified as positive [≥0.63 pg/mL], intermediate [0.40-0.62 pg/mL], and negative [<0.40 pg/mL]), Aβ–positron emission tomography (PET; 18 F-florbetapir; with Aβ-positive defined as a standardized uptake value ratio [SUVR] ≥1.10), and tau-PET ( 18 F-flortaucipir). TES diagnoses were assigned by multidisciplinary consensus conference. Analyses of postmortem brains controlled for age, race, and APOE ε4 status. Results Among 231 participants (mean [SD] age, 57.75 [8.25] years), 177 were former football players (117 professional and 60 college) and 54 were unexposed participants. Former football players had higher baseline mean (SD) p-tau217 concentrations than unexposed participants (0.35 [0.26] pg/mL vs 0.27 [0.14] pg/mL; P = .008), although this was driven by a higher proportion of Aβ-PET–positive participants among former players. Plasma p-tau217 increased over time across the sample (B = 0.207 [95% CI, 0.117-0.298]; P < .001), with no significant time × exposure group interactions. Among football players, p-tau217 showed no time × group interactions with TES diagnosis, TES-CTE certainty, or RHI metrics. Higher p-tau217 concentration correlated with higher global Aβ-PET SUVR (B = 0.058 [95% CI, 0.053-3.501; P = .01), with a few discordant cases (5 participants were p-tau217–negative and Aβ-PET–positive; 7 participants were p-tau217–positive and Aβ-PET–negative). P-tau217 had similar areas under the curve for projecting Aβ-PET positivity as cerebrospinal fluid (CSF) p-tau181/Aβ42 and CSF Aβ40/42 measures (p-tau217: AUC, 0.88 [95% CI, 0.80-0.96]; CSF p-tau181/Aβ42: AUC, 0.89 [95% CI, 0.79-1.00]; CSF Aβ40/42: AUC, 0.85 [95% CI, 0.72-0.98]). Among 9 brain donors, 6 had CTE (stages II-IV; none with Alzheimer disease). Seven had negative or intermediate p-tau217, concordant with Aβ-PET. Two p-tau217 outliers with stage III CTE had normal concentrations upon additional testing. Conclusions and Relevance The findings of this study suggest that plasma p-tau217 concentration is unlikely to be useful for the detection of CTE, but it does show utility for ruling out Aβ pathology in participants at risk for CTE.
Imaging the later‐life white matter pathologies of repetitive head impacts: A novel pattern revealed through T2 FLAIR MRI
Groh, Jenna R. , Miner, Annalise E., Alshikho, Mohamad J. , Farris, Chad, Cui, Anna, Pettway, Erika, Labonte, Jacob , Mosaheb, Sydney, Tripodis, Yorghos, Adler, Charles H., Balcer, Laura J. , Bernick, Charles, Cantu, Robert C., Dodick, David W., Ashton, Nicholas J., Zetterberg, Henrik, Blennow, Kaj, Peskind, Elaine R. , Nowinski, Christopher, Lenio, Steven, Rabinovici, Gil D., Asken, Breton, Rosen, Howard, Blusztajn, Jan Krzysztof , Budson, Andrew E., Turk, Katherine, Goldstein, Lee, Martin, Brett, Palmisano, Joseph N., Dixon, Diane, Schneider, Greta, Steinberg, Eric G., Su, Yi, Protas, Hillary , Pasternak, Ofer, Bouix, Sylvain, Cummings, Jeffrey L., Reiman, Eric M., Shenton, Martha E., Stern, Robert A., McKee, Ann C., Stein, Thor D., Brickman, Adam M., Mez, Jesse, Alosco, Michael L., Rabinovici, Gil D. , Rabinovici, Gil D , Miner, Annalise E., Farris, Chad W. , Cui, Anna, Pettway, Erika C, Tripodis, Yorghos , Adler, Charles H. , Bernick, Charles , Cantu, Robert C. , Coleman, Michael , Dodick, David W. , Ashton, Nicholas J. , Zetterberg, Henrik , Blennow, Kaj , Ly, Monica T. , Altaras, Caroline , Lenio, Steven , Asken, Breton M. , Cobigo, Yann , Budson, Andrew E. , Turk, Katherine W. , Qiu, Wei Qiao , Palmisano, Joseph , Steinberg, Eric G. , Pasternak, Ofer , Koerte, Inga K , Bouix, Sylvain , Reiman, Eric M. , Shenton, Martha E. , McKee, Ann C. , Stein, Thor D. , Brickman, Adam M. , Mez, Jesse , Alosco, Michael L.
Alzheimer's & Dementia | April 20, 2026 | Volume: 22 | Issue: 4 | Pages: No page available
Abstract INTRODUCTION Repetitive head impacts (RHI) from contact sports may cause a unique pattern of white matter hyperintensities (WMH) on T2‐weighted fluid‐attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), termed RHI‐associated WMH (RHI‐WMH). These lesions are punctate, circular, and located at the gray–white matter boundary, an area vulnerable to trauma‐related damage. METHODS We investigated the association of RHI with these lesions in two aging cohorts: (1) former American football players versus asymptomatic unexposed men and (2) individuals with RHI from various contact sports versus non‐RHI participants. RHI‐WMH were assessed using visual ratings and a novel automated quantification pipeline. RESULTS Individuals with RHI had greater RHI‐WMH by both detection methods in both cohorts. RHI‐WMH were associated with plasma neurofilament light and p‐tau231, and flortaucipir positron emission tomography (PET) uptake. DISCUSSION RHI‐WMH may represent a new supportive biomarker for the detection of RHI‐related neuropathologies later in life.