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1. Inflammatory biomarkers for neurobehavioral dysregulation in former American football players: findings from the DIAGNOSE CTE Research Project

Author

van Amerongen, Suzan, Pulukuri, Surya V., Tuz-Zahra, Fatima, Tripodis, Yorghos, Cherry, Jonathan D., Bernick, Charles, Geda, Yonas E., Wethe, Jennifer V., Katz, Douglas I., Alosco, Michael L., Adler, Charles H., Balcer, Laura J., Ashton, Nicholas J., Blennow, Kaj, Zetterberg, Henrik, Daneshvar, Daniel H., Colasurdo, Elizabeth A., Iliff, Jeffrey J., Li, Gail, Peskind, Elaine R., Shenton, Martha E., Reiman, Eric M., Cummings, Jeffrey L., and Stern, Robert A.

Published
2024
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2. Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players

Author

Alosco, Michael L, Su, Yi, Stein, Thor D, Protas, Hillary, Cherry, Jonathan D, Adler, Charles H, Balcer, Laura J, Bernick, Charles, Pulukuri, Surya Vamsi, Abdolmohammadi, Bobak, Coleman, Michael J, Palmisano, Joseph N, Tripodis, Yorghos, Mez, Jesse, Rabinovici, Gil D, Marek, Kenneth L, Beach, Thomas G, Johnson, Keith A, Huber, Bertrand Russell, Koerte, Inga, Lin, Alexander P, Bouix, Sylvain, Cummings, Jeffrey L, Shenton, Martha E, Reiman, Eric M, McKee, Ann C, and Stern, Robert A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Aging, Physical Injury - Accidents and Adverse Effects, Acquired Cognitive Impairment, Brain Disorders, Alzheimer's Disease, Dementia, Neurosciences, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurological, Humans, Alzheimer Disease, Autopsy, Brain, Brain Injuries, Traumatic, Chronic Traumatic Encephalopathy, Death, Football, Positron-Emission Tomography, tau Proteins, Biomarkers, Chronic traumatic encephalopathy, Neurodegenerative disease, Positron emission tomography imaging, Repetitive head impacts, Tau, Flortaucipir, DIAGNOSE C. T. E. Research Project, Other Physical Sciences, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract

PurposeFlourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer's disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players.MethodsThree former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs).ResultsFour brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions.ConclusionsFlortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.

Published
2023

3. Differential Vulnerability of Hippocampal Subfields in Primary Age-Related Tauopathy and Chronic Traumatic Encephalopathy.

Author

Farrell, Kurt, Iida, Megan A, Cherry, Jonathan D, Casella, Alicia, Stein, Thor D, Bieniek, Kevin F, Walker, Jamie M, Richardson, Timothy E, White, Charles L, Alvarez, Victor E, Huber, Bertrand R, Dickson, Dennis W, Insausti, Ricardo, Dams-O'Connor, Kristen, Vonsattel, Jean-Paul, Teich, Andy F, Gearing, Marla, Glass, Jonathan, Troncoso, Juan C, Frosch, Matthew P, Hyman, Bradley T, Murray, Melissa E, Attems, Johannes, Flanagan, Margaret E, Mao, Qinwen, Mesulam, M-Marsel, Weintraub, Sandra, Woltjer, Randy L, Pham, Thao, Kofler, Julia, Schneider, Julie A, Yu, Lei, Purohit, Dushyant P, Haroutunian, Vahram, Hof, Patrick R, Gandy, Sam, Sano, Mary, Beach, Thomas G, Poon, Wayne, Kawas, Claudia H, Corrada, María M, Rissman, Robert A, Metcalf, Jeff, Shuldberg, Sara, Salehi, Bahar, Nelson, Peter T, Trojanowski, John Q, Lee, Edward B, Wolk, David A, McMillan, Corey T, Keene, C Dirk, Latimer, Caitlin S, Montine, Thomas J, Kovacs, Gabor G, Lutz, Mirjam I, Fischer, Peter, Perrin, Richard J, Cairns, Nigel J, McKee, Ann C, and Crary, John F

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Frontotemporal Dementia (FTD), Acquired Cognitive Impairment, Aging, Brain Disorders, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Chronic Traumatic Encephalopathy, Hippocampus, Humans, Neurofibrillary Tangles, Tauopathies, tau Proteins, Chronic traumatic encephalopathy, Primary age-related tauopathy, Repetitive head impacts, Tauopathy, Part Working Group, Neurology & Neurosurgery, Clinical sciences
Abstract

Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repetitive mild head impacts characterized by perivascular hyperphosphorylated tau (p-tau) in neurofibrillary tangles (NFTs) and neurites in the depths of the neocortical sulci. In moderate to advanced CTE, NFTs accumulate in the hippocampus, potentially overlapping neuroanatomically with primary age-related tauopathy (PART), an age-related tauopathy characterized by Alzheimer disease-like tau pathology in the hippocampus devoid of amyloid plaques. We measured p-tau burden using positive-pixel counts on immunohistochemically stained and neuroanatomically segmented hippocampal tissue. Subjects with CTE had a higher total p-tau burden than PART subjects in all sectors (p = 0.005). Within groups, PART had significantly higher total p-tau burden in CA1/subiculum compared to CA3 (p = 0.02) and CA4 (p = 0.01) and total p-tau burden in CA2 trended higher than CA4 (p = 0.06). In CTE, total p-tau burden in CA1/subiculum was significantly higher than in the dentate gyrus; and CA2 also trended higher than dentate gyrus (p = 0.01, p = 0.06). When controlling for p-tau burden across the entire hippocampus, CA3 and CA4 had significantly higher p-tau burden in CTE than PART (p

Published
2022

5. Leveraging football accelerometer data to quantify associations between repetitive head impacts and chronic traumatic encephalopathy in males

Author

Daneshvar, Daniel H., Nair, Evan S., Baucom, Zachary H., Rasch, Abigail, Abdolmohammadi, Bobak, Uretsky, Madeline, Saltiel, Nicole, Shah, Arsal, Jarnagin, Johnny, Baugh, Christine M., Martin, Brett M., Palmisano, Joseph N., Cherry, Jonathan D., Alvarez, Victor E., Huber, Bertrand R., Weuve, Jennifer, Nowinski, Christopher J., Cantu, Robert C., Zafonte, Ross D., Dwyer, Brigid, Crary, John F., Goldstein, Lee E., Kowall, Neil W., Katz, Douglas I., Stern, Robert A., Tripodis, Yorghos, Stein, Thor D., McClean, Michael D., Alosco, Michael L., McKee, Ann C., and Mez, Jesse

Published
2023
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6. Genome-wide association study and functional validation implicates JADE1 in tauopathy

Author

Farrell, Kurt, Kim, SoongHo, Han, Natalia, Iida, Megan A, Gonzalez, Elias M, Otero-Garcia, Marcos, Walker, Jamie M, Richardson, Timothy E, Renton, Alan E, Andrews, Shea J, Fulton-Howard, Brian, Humphrey, Jack, Vialle, Ricardo A, Bowles, Kathryn R, de Paiva Lopes, Katia, Whitney, Kristen, Dangoor, Diana K, Walsh, Hadley, Marcora, Edoardo, Hefti, Marco M, Casella, Alicia, Sissoko, Cheick T, Kapoor, Manav, Novikova, Gloriia, Udine, Evan, Wong, Garrett, Tang, Weijing, Bhangale, Tushar, Hunkapiller, Julie, Ayalon, Gai, Graham, Robert R, Cherry, Jonathan D, Cortes, Etty P, Borukov, Valeriy Y, McKee, Ann C, Stein, Thor D, Vonsattel, Jean-Paul, Teich, Andy F, Gearing, Marla, Glass, Jonathan, Troncoso, Juan C, Frosch, Matthew P, Hyman, Bradley T, Dickson, Dennis W, Murray, Melissa E, Attems, Johannes, Flanagan, Margaret E, Mao, Qinwen, Mesulam, M-Marsel, Weintraub, Sandra, Woltjer, Randy L, Pham, Thao, Kofler, Julia, Schneider, Julie A, Yu, Lei, Purohit, Dushyant P, Haroutunian, Vahram, Hof, Patrick R, Gandy, Sam, Sano, Mary, Beach, Thomas G, Poon, Wayne, Kawas, Claudia H, Corrada, María M, Rissman, Robert A, Metcalf, Jeff, Shuldberg, Sara, Salehi, Bahar, Nelson, Peter T, Trojanowski, John Q, Lee, Edward B, Wolk, David A, McMillan, Corey T, Keene, C Dirk, Latimer, Caitlin S, Montine, Thomas J, Kovacs, Gabor G, Lutz, Mirjam I, Fischer, Peter, Perrin, Richard J, Cairns, Nigel J, Franklin, Erin E, Cohen, Herbert T, Raj, Towfique, Cobos, Inma, Frost, Bess, Goate, Alison, White III, Charles L, and Crary, John F

Subjects
Biomedical and Clinical Sciences, Neurosciences, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Genetics, Dementia, Acquired Cognitive Impairment, Frontotemporal Dementia (FTD), Aging, Alzheimer's Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Animals, Cohort Studies, Drosophila, Female, Genome-Wide Association Study, Homeodomain Proteins, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Tauopathies, Tumor Suppressor Proteins, Clinical Sciences, Neurology & Neurosurgery
Abstract

Primary age-related tauopathy (PART) is a neurodegenerative pathology with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-β (Aβ) plaques. The pathogenesis of PART is not known, but evidence suggests an association with genes that promote tau pathology and others that protect from Aβ toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n = 647) using Braak neurofibrillary tangle stage as a quantitative trait. We found some significant associations with candidate loci associated with AD (SLC24A4, MS4A6A, HS3ST1) and progressive supranuclear palsy (MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brains with four microtubule-binding domain repeats (4R) isoforms and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation in post-mortem human PART brain tissue revealed a specific binding of JADE1 protein to four repeat tau lacking N-terminal inserts (0N4R). Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model, as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a modifier of neurofibrillary degeneration.

Published
2022

8. Repetitive head impacts and chronic traumatic encephalopathy are associated with TDP-43 inclusions and hippocampal sclerosis

Author

Nicks, Raymond, Clement, Nathan F., Alvarez, Victor E., Tripodis, Yorghos, Baucom, Zachery H., Huber, Bertrand R., Mez, Jesse, Alosco, Michael L., Aytan, Nurgul, Cherry, Jonathan D., Cormier, Kerry A., Kubilius, Carol, Mathias, Rebecca, Svirsky, Sarah E., Pothast, Morgan J., Hildebrandt, Audrey M., Chung, Jaeyoon, Han, Xudong, Crary, John F., McKee, Ann C., Frosch, Matthew P., and Stein, Thor D.

Published
2023
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9. Genome-wide association study and functional validation implicates JADE1 in tauopathy

Author

Farrell, Kurt, Kim, SoongHo, Han, Natalia, Iida, Megan A, Gonzalez, Elias, Otero-Garcia, Marcos, Walker, Jamie, Richardson, Tim, Renton, Alan E, Andrews, Shea J, Fulton-Howard, Brian, Humphrey, Jack, Vialle, Ricardo A, Bowles, Kathryn R, Whitney, Kristen, Dangoor, Diana K, Marcora, Edoardo, Hefti, Marco M, Casella, Alicia, Sissoko, Cheick, Kapoor, Manav, Novikova, Gloriia, Udine, Evan, Wong, Garrett, Tang, Weijing, Bhangale, Tushar, Hunkapiller, Julie, Ayalon, Gai, Graham, Rob, Cherry, Jonathan D, Cortes, Etty, Borukov, Valeriy, McKee, Ann C, Stein, Thor D, Vonsattel, Jean-Paul, Teich, Andy F, Gearing, Marla, Glass, Jonathan, Troncoso, Juan C, Frosch, Matthew P, Hyman, Bradley T, Dickson, Dennis W, Murray, Melissa E, Attems, Johannes, Flanagan, Margaret E, Mao, Qinwen, Mesulam, M-Marsel, Weintraub, Sandra, Woltjer, Randy, Pham, Thao, Kofler, Julia, Schneider, Julie A, Yu, Lei, Purohit, Dushyant P, Haroutunian, Vahram, Hof, Patrick R, Gandy, Sam, Sano, Mary, Beach, Thomas G, Poon, Wayne, Kawas, Claudia, Corrada, María, Rissman, Robert A, Metcalf, Jeff, Shuldberg, Sara, Salehi, Bahar, Nelson, Peter T, Trojanowski, John Q, Lee, Edward B, Wolk, David A, McMillan, Corey T, Keene, Dirk C, Montine, Thomas J, Kovacs, Gabor G, Lutz, Mirjam I, Fischer, Peter, Perrin, Richard J, Cairns, Nigel, Franklin, Erin E, Cohen, Herbert T, Sillero, Maria Inmaculada Cobos, Frost, Bess, Raj, Towfique, Goate, Alison, White, Charles L, and Crary, John F

Subjects
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Genetics, Dementia, Alzheimer's Disease, Frontotemporal Dementia (FTD), Brain Disorders, Neurosciences, Biotechnology, Neurodegenerative, Aging, Acquired Cognitive Impairment, Aetiology, 2.1 Biological and endogenous factors, Neurological
Abstract

AbstractPrimary age-related tauopathy (PART) is a neurodegenerative tauopathy with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-β (Aβ) deposition in plaques. The pathogenesis of PART is unknown, but evidence suggests it is associated with genes that promote tau pathology as well as others that protect from Aβ toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n=647) using Braak neurofibrillary tangle stage as a quantitative trait adjusting for sex, age, genotyping platform, and principal components. We found significant associations with some candidate loci associated with AD and progressive supranuclear palsy, a primary tauopathy (SLC24A4, MS4A6A, HS3ST1, MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brain from tauopathies containing isoforms with four microtubule-binding domain repeats (4R) and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation revealed a direct and specific binding of JADE1 protein to tau containing four (4R) and no N-terminal inserts (0N4R) in post-mortem human PART brain tissue. Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a mediator of neurofibrillary degeneration.

Published
2021

13. A comparison between tau and amyloid-β cerebrospinal fluid biomarkers in chronic traumatic encephalopathy and Alzheimer disease

Author

Turk, Katherine W., Geada, Alexandra, Alvarez, Victor E., Xia, Weiming, Cherry, Jonathan D., Nicks, Raymond, Meng, Gaoyuan, Daley, Sarah, Tripodis, Yorghos, Huber, Bertrand R., Budson, Andrew E., Dwyer, Brigid, Kowall, Neil W., Cantu, Robert C., Goldstein, Lee E., Katz, Douglas I., Stern, Robert A., Alosco, Michael L., Mez, Jesse, McKee, Ann C., and Stein, Thor D.

Published
2022
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14. 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Published
2022
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15. Substantia Nigra Pathology, Contact Sports Play, and Parkinsonism in Chronic Traumatic Encephalopathy.

Author

Adams, Jason W., Kirsch, Daniel, Calderazzo, Samantha M., Tuz-Zahra, Fatima, Tripodis, Yorghos, Mez, Jesse, Alosco, Michael L., Alvarez, Victor E., Huber, Bertrand R., Kubilus, Caroline, Cormier, Kerry A., Nicks, Raymond, Uretsky, Madeline, Nair, Evan, Kuzyk, Eva, Aytan, Nurgul, Cherry, Jonathan D., Crary, John F., Daneshvar, Daniel H., and Nowinski, Christopher J.

Published
2024
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17. Repetitive head impacts induce neuronal loss and neuroinflammation in young athletes

Author

Butler, Morgane L.M.D., primary, Pervaiz, Nida, additional, Ypsilantis, Petra, additional, Wang, Yichen, additional, Breda, Julia C, additional, Mazzilli, Sarah A, additional, Nicks, Raymond, additional, Spurlock, Elizabeth, additional, Hefti, Marco M, additional, Huber, Bertrand R, additional, Alvarez, Victor E, additional, Stein, Thor D, additional, Campbell, Joshua D, additional, McKee, Ann C, additional, and Cherry, Jonathan D, additional

Published
2024
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18. MAPT subhaplotypes and chronic traumatic encephalopathy

Author

Han, Xudong, primary, Petrosky, Jillian, additional, Bald, Sarah, additional, Zhang, Yichi, additional, Sherva, Richard, additional, Chung, Jaeyoon, additional, Abdolmohammadi, Bobak, additional, Durape, Shruti, additional, Martin, Brett M, additional, Palmisano, Joseph N, additional, Farrell, Kurt W., additional, Farrell, John, additional, Cherry, Jonathan D, additional, Alvarez, Victor E., additional, Huber, Bertrand R., additional, Alosco, Michael L, additional, Tripodis, Yorghos, additional, Stern, Robert A, additional, Stein, Thor D., additional, Farrer, Lindsay A., additional, Crary, John F., additional, McKee, Ann C., additional, and Mez, Jesse B., additional

Published
2023
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19. Neuroimmune proteins can differentiate between distinct neurodegenerative diseases

Author

Cherry, Jonathan D, primary, Baucom, Zachary H., additional, Eppich, Kaleb G, additional, Kirsch, Daniel A, additional, Dixon, Erin R, additional, Tripodis, Yorghos, additional, Bieniek, Kevin F, additional, Farrell, Kurt W., additional, Whitney, Kristen R., additional, Uretsky, Madeline, additional, Crary, John F., additional, Dickson, Dennis W., additional, and McKee, Ann C., additional

Published
2023
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20. Association of probable REM sleep behavior disorder with pathology and years of contact sports play in chronic traumatic encephalopathy

Author

Adams, Jason W., Alosco, Michael L., Mez, Jesse, Alvarez, Victor E., Huber, Bertrand R., Tripodis, Yorghos, Adler, Charles H., Kubilius, Carol, Cormier, Kerry A., Mathais, Rebecca, Nicks, Raymond, Kelley, Hunter J., Saltiel, Nicole, Uretsky, Madeline, Nair, Evan, Aytan, Nurgul, Cherry, Jonathan D., Nowinski, Christopher J., Kowall, Neil W., Goldstein, Lee E., Dwyer, Brigid, Katz, Douglas I., Cantu, Robert C., Stern, Robert A., McKee, Ann C., and Stein, Thor D.

Published
2020
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22. Characterizing tau deposition in chronic traumatic encephalopathy (CTE): utility of the McKee CTE staging scheme

Author

Alosco, Michael L., Cherry, Jonathan D., Huber, Bertrand Russell, Tripodis, Yorghos, Baucom, Zachary, Kowall, Neil W., Saltiel, Nicole, Goldstein, Lee E., Katz, Douglas I., Dwyer, Brigid, Daneshvar, Daniel H., Palmisano, Joseph N., Martin, Brett, Cantu, Robert C., Stern, Robert A., Alvarez, Victor E., Mez, Jesse, Stein, Thor D., and McKee, Ann C.

Published
2020
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23. Neuropathologic and Clinical Findings in Young Contact Sport Athletes Exposed to Repetitive Head Impacts

Author

McKee, Ann C., primary, Mez, Jesse, additional, Abdolmohammadi, Bobak, additional, Butler, Morgane, additional, Huber, Bertrand Russell, additional, Uretsky, Madeline, additional, Babcock, Katharine, additional, Cherry, Jonathan D., additional, Alvarez, Victor E., additional, Martin, Brett, additional, Tripodis, Yorghos, additional, Palmisano, Joseph N., additional, Cormier, Kerry A., additional, Kubilus, Caroline A., additional, Nicks, Raymond, additional, Kirsch, Daniel, additional, Mahar, Ian, additional, McHale, Lisa, additional, Nowinski, Christopher, additional, Cantu, Robert C., additional, Stern, Robert A., additional, Daneshvar, Daniel, additional, Goldstein, Lee E., additional, Katz, Douglas I., additional, Kowall, Neil W., additional, Dwyer, Brigid, additional, Stein, Thor D., additional, and Alosco, Michael L., additional

Published
2023
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25. Contact sport participation and chronic traumatic encephalopathy are associated with altered severity and distribution of cerebral amyloid angiopathy

Author

Standring, Oliver J., Friedberg, Jacob, Tripodis, Yorghos, Chua, Alicia S., Cherry, Jonathan D., Alvarez, Victor E., Huber, Bertrand R., Xia, Weiming, Mez, Jesse, Alosco, Michael L., Nicks, Raymond, Mahar, Ian, Pothast, Morgan J., Gardner, Hannah M., Meng, Gaoyuan, Palmisano, Joseph N., Martin, Brett M., Dwyer, Brigid, Kowall, Neil W., Cantu, Robert C., Goldstein, Lee E., Katz, Douglas I., Stern, Robert A., McKee, Ann C., and Stein, Thor D.

Published
2019
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28. Vascular injury is associated with repetitive head impacts and tau pathology in chronic traumatic encephalopathy

Author

Kirsch, Daniel, primary, Shah, Arsal, additional, Dixon, Erin, additional, Kelley, Hunter, additional, Cherry, Jonathan D, additional, Xia, Weiming, additional, Daley, Sarah, additional, Aytan, Nurgul, additional, Cormier, Kerry, additional, Kubilus, Carol, additional, Mathias, Rebecca, additional, Alvarez, Victor E, additional, Huber, Bertrand R, additional, McKee, Ann C, additional, and Stein, Thor D, additional

Published
2023
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29. Variation in TMEM106B in chronic traumatic encephalopathy

Author

Cherry, Jonathan D., Mez, Jesse, Crary, John F., Tripodis, Yorghos, Alvarez, Victor E., Mahar, Ian, Huber, Bertrand R., Alosco, Michael L., Nicks, Raymond, Abdolmohammadi, Bobak, Kiernan, Patrick T., Evers, Laney, Svirsky, Sarah, Babcock, Katharine, Gardner, Hannah M., Meng, Gaoyuan, Nowinski, Christopher J., Martin, Brett M., Dwyer, Brigid, Kowall, Neil W., Cantu, Robert C., Goldstein, Lee E., Katz, Douglas I., Stern, Robert A., Farrer, Lindsay A., McKee, Ann C., and Stein, Thor D.

Published
2018
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30. Leveraging American football helmet accelerometer data to estimate associations between cumulative repetitive head impact exposure and chronic traumatic encephalopathy

Author

Nair, Evan S, primary, Daneshvar, Daniel H, additional, Rasch, Abigail, additional, Abdolmohammadi, Bobak, additional, Saltiel, Nicole, additional, Uretsky, Madeline, additional, Shah, Arsal, additional, Baucom, Zachary H., additional, Martin, Brett M, additional, Palmisano, Joseph, additional, Cherry, Jonathan D, additional, Alvarez, Victor E., additional, Huber, Bertrand R., additional, Alosco, Michael L, additional, Tripodis, Yorghos, additional, Crary, John F., additional, Stein, Thor D., additional, McKee, Ann C., additional, and Mez, Jesse B., additional

Published
2022
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31. Neuroimmune proteins can differentiate between tauopathies

Author

Cherry, Jonathan D., primary, Baucom, Zach H., additional, Eppich, Kaleb G., additional, Kirsch, Daniel, additional, Dixon, Erin R., additional, Tripodis, Yorghos, additional, Bieniek, Kevin F., additional, Farrell, Kurt, additional, Whitney, Kristen, additional, Uretsky, Madeline, additional, Crary, John F., additional, Dickson, Dennis, additional, and McKee, Ann C., additional

Published
2022
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32. Association of APOE Genotypes and Chronic Traumatic Encephalopathy

Author

Atherton, Kathryn, primary, Han, Xudong, additional, Chung, Jaeyoon, additional, Cherry, Jonathan D., additional, Baucom, Zachary, additional, Saltiel, Nicole, additional, Nair, Evan, additional, Abdolmohammadi, Bobak, additional, Uretsky, Madeline, additional, Khan, Mohammed Muzamil, additional, Shea, Conor, additional, Durape, Shruti, additional, Martin, Brett M., additional, Palmisano, Joseph N., additional, Farrell, Kurt, additional, Nowinski, Christopher J., additional, Alvarez, Victor E., additional, Dwyer, Brigid, additional, Daneshvar, Daniel H., additional, Katz, Douglas I., additional, Goldstein, Lee E., additional, Cantu, Robert C., additional, Kowall, Neil W., additional, Alosco, Michael L., additional, Huber, Bertrand R., additional, Tripodis, Yorghos, additional, Crary, John F., additional, Farrer, Lindsay, additional, Stern, Robert A., additional, Stein, Thor D., additional, McKee, Ann C., additional, and Mez, Jesse, additional

Published
2022
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33. Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players

Author

Alosco, Michael L, Su, Yi, Stein, Thor D, Protas, Hillary, Cherry, Jonathan D, Adler, Charles H, Balcer, Laura J, Bernick, Charles, Pulukuri, Surya Vamsi, Abdolmohammadi, Bobak, Coleman, Michael J, Palmisano, Joseph N, Tripodis, Yorghos, Mez, Jesse, Rabinovici, Gil D, Marek, Kenneth L, Beach, Thomas G, Johnson, Keith A, Huber, Bertrand Russell, Koerte, Inga, Lin, Alexander P, Bouix, Sylvain, Cummings, Jeffrey L, Shenton, Martha E, Reiman, Eric M, McKee, Ann C, Stern, Robert A, and DIAGNOSE C. T. E. Research Project

Subjects
Traumatic, Aging, Physical Injury - Accidents and Adverse Effects, DIAGNOSE C. T. E. Research Project, Clinical Sciences, Football, tau Proteins, Neurodegenerative, Neurodegenerative disease, Alzheimer's Disease, Chronic Traumatic Encephalopathy, Alzheimer Disease, Acquired Cognitive Impairment, Humans, Positron emission tomography imaging, Flortaucipir, Neurosciences, Brain, Repetitive head impacts, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Death, Other Physical Sciences, Nuclear Medicine & Medical Imaging, Positron-Emission Tomography, Brain Injuries, Neurological, Dementia, Autopsy, Tau, Biomarkers
Abstract

PurposeFlourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer's disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players.MethodsThree former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs).ResultsFour brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions.ConclusionsFlortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.

Published
2022

36. Additional file 1 of Neuroimmune proteins can differentiate between tauopathies

Author

Cherry, Jonathan D., Baucom, Zach H., Eppich, Kaleb G., Kirsch, Daniel, Dixon, Erin R., Tripodis, Yorghos, Bieniek, Kevin F., Farrell, Kurt, Whitney, Kristen, Uretsky, Madeline, Crary, John F., Dickson, Dennis, and McKee, Ann C.

Abstract

Additional file 1: Figure S1. CCL21 is still elevated in the CTE CSF in the male subset of cases. To determine if gender was driving the CSF related CCL21 elevation, only males from the CTE and AD groups were compared. Although the AD male sample size was reduced to 5 cases, CCL21 concentrations still trended towards significant increases in CTE as measured with a Mann–Whitney test. Each dot represents 1 case. Error bars represent mean ± SEM.

Published
2022
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37. Additional file 5 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 5. Supplementary fig 5

Published
2022
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38. Additional file 2 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 2. Supplementary fig 2

Published
2022
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39. Additional file 10 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 10. Supplementary table 3

Published
2022
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40. Additional file 3 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 3. Supplementary fig 3

Published
2022
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41. Additional file 4 of A comparison between tau and amyloid-�� cerebrospinal fluid biomarkers in chronic traumatic encephalopathy and Alzheimer disease

Author

Turk, Katherine W., Geada, Alexandra, Alvarez, Victor E., Xia, Weiming, Cherry, Jonathan D., Nicks, Raymond, Meng, Gaoyuan, Daley, Sarah, Tripodis, Yorghos, Huber, Bertrand R., Budson, Andrew E., Dwyer, Brigid, Kowall, Neil W., Cantu, Robert C., Goldstein, Lee E., Katz, Douglas I., Stern, Robert A., Alosco, Michael L., Mez, Jesse, McKee, Ann C., and Stein, Thor D.

Abstract

Additional file 4: Table e-1. Estimated Marginal Means and SEM in parentheses for rank normalized CSF analyte measurements from No CTE/no AD (control) group; showing ANCOVA adjusted for age, p

Published
2022
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42. Additional file 7 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 7. Supplementary fig 7

Published
2022
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43. Additional file 6 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 6. Supplementary fig 6

Published
2022
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45. Additional file 4 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 4. Supplementary fig 4

Published
2022
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46. Additional file 9 of 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

Author

Bowles, Kathryn R., Pugh, Derian A., Liu, Yiyuan, Patel, Tulsi, Renton, Alan E., Bandres-Ciga, Sara, Gan-Or, Ziv, Heutink, Peter, Siitonen, Ari, Bertelsen, Sarah, Cherry, Jonathan D., Karch, Celeste M., Frucht, Steven J., Kopell, Brian H., Peter, Inga, Park, Y. J., Charney, Alexander, Raj, Towfique, Crary, John F., and Goate, A. M.

Abstract

Additional file 9. Supplementary table 2

Published
2022
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47. Additional file 1 of A comparison between tau and amyloid-�� cerebrospinal fluid biomarkers in chronic traumatic encephalopathy and Alzheimer disease

Author

Turk, Katherine W., Geada, Alexandra, Alvarez, Victor E., Xia, Weiming, Cherry, Jonathan D., Nicks, Raymond, Meng, Gaoyuan, Daley, Sarah, Tripodis, Yorghos, Huber, Bertrand R., Budson, Andrew E., Dwyer, Brigid, Kowall, Neil W., Cantu, Robert C., Goldstein, Lee E., Katz, Douglas I., Stern, Robert A., Alosco, Michael L., Mez, Jesse, McKee, Ann C., and Stein, Thor D.

Abstract

Additional file 1. Supplemental results

Published
2022
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49. Dysregulated coordination of MAPT exon 2 and exon 10 splicing underlies different tau pathologies in PSP and AD

Author

Bowles, Kathryn R., primary, Pugh, Derian A., additional, Oja, Laura-Maria, additional, Jadow, Benjamin M., additional, Farrell, Kurt, additional, Whitney, Kristen, additional, Sharma, Abhijeet, additional, Cherry, Jonathan D., additional, Raj, Towfique, additional, Pereira, Ana C., additional, Crary, John F., additional, and Goate, Alison M., additional

Published
2021
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50. Tau phosphorylation sites serine202 and serine396 are differently altered in chronic traumatic encephalopathy and Alzheimer's disease

Author

Stathas, SpiroAnthony, primary, Alvarez, Victor E., additional, Xia, Weiming, additional, Nicks, Raymond, additional, Meng, Gaoyuan, additional, Daley, Sarah, additional, Pothast, Morgan, additional, Shah, Arsal, additional, Kelley, Hunter, additional, Esnault, Camille, additional, McCormack, Robert, additional, Dixon, Erin, additional, Fishbein, Lucas, additional, Cherry, Jonathan D., additional, Huber, Bertrand R., additional, Tripodis, Yorghos, additional, Alosco, Michael L., additional, Mez, Jesse, additional, McKee, Ann C., additional, and Stein, Thor D., additional

Published
2021
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