Search

Your search keyword '"Mckee, Ann C."' showing total 1,110 results
Start Over Author "Mckee, Ann C."
1,110 results on '"Mckee, Ann C."'

301. Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy

Author

Seo, Jeong-Sun, primary, Lee, Seungbok, additional, Shin, Jong-Yeon, additional, Hwang, Yu Jin, additional, Cho, Hyesun, additional, Yoo, Seong-Keun, additional, Kim, Yunha, additional, Lim, Sungsu, additional, Kim, Yun Kyung, additional, Hwang, Eun Mi, additional, Kim, Su Hyun, additional, Kim, Chong-Hyun, additional, Hyeon, Seung Jae, additional, Yun, Ji-Young, additional, Kim, Jihye, additional, Kim, Yona, additional, Alvarez, Victor E, additional, Stein, Thor D, additional, Lee, Junghee, additional, Kim, Dong Jin, additional, Kim, Jong-Il, additional, Kowall, Neil W, additional, Ryu, Hoon, additional, and McKee, Ann C, additional

Published
2017
Full Text
View/download PDF

302. Modeling the Relationships Among Late-Life Body Mass Index, Cerebrovascular Disease, and Alzheimer’s Disease Neuropathology in an Autopsy Sample of 1,421 Subjects from the National Alzheimer’s Coordinating Center Data Set

Author

Alosco, Michael L., primary, Duskin, Jonathan, additional, Besser, Lilah M., additional, Martin, Brett, additional, Chaisson, Christine E., additional, Gunstad, John, additional, Kowall, Neil W., additional, McKee, Ann C., additional, Stern, Robert A., additional, and Tripodis, Yorghos, additional

Published
2017
Full Text
View/download PDF

305. Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players

Author

Montenigro, Philip H., primary, Alosco, Michael L., additional, Martin, Brett M., additional, Daneshvar, Daniel H., additional, Mez, Jesse, additional, Chaisson, Christine E., additional, Nowinski, Christopher J., additional, Au, Rhoda, additional, McKee, Ann C., additional, Cantu, Robert C., additional, McClean, Michael D., additional, Stern, Robert A., additional, and Tripodis, Yorghos, additional

Published
2017
Full Text
View/download PDF

306. Cognitive Reserve as a Modifier of Clinical Expression in Chronic Traumatic Encephalopathy: A Preliminary Examination

Author

Alosco, Michael L., primary, Mez, Jesse, additional, Kowall, Neil W., additional, Stein, Thor D., additional, Goldstein, Lee E., additional, Cantu, Robert C., additional, Katz, Douglas I., additional, Solomon, Todd M., additional, Kiernan, Patrick T., additional, Murphy, Lauren, additional, Abdolmohammadi, Bobak, additional, Daneshvar, Daniel, additional, Montenigro, Philip H., additional, Nowinski, Christopher J., additional, Stern, Robert A., additional, and McKee, Ann C., additional

Published
2017
Full Text
View/download PDF

307. A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI

Author

Iglesias, Juan Eugenio, Augustinack, Jean C, Nguyen, Khoa, Player, Christopher M, Player, Allison, Wright, Michelle, Roy, Nicole, Frosch, Matthew P, McKee, Ann C, Wald, Lawrence L, Fischl, Bruce, Van Leemput, Koen, and Alzheimer's Disease Neuroimaging Initiative

Subjects
Male, Image Processing, Bioengineering, Hippocampus, Medical and Health Sciences, Computer-Assisted, Atlases as Topic, Alzheimer Disease, Diagnosis, 80 and over, Acquired Cognitive Impairment, Humans, Cognitive Dysfunction, Aged, Neurology & Neurosurgery, Psychology and Cognitive Sciences, Alzheimer's Disease Neuroimaging Initiative, Neurosciences, Brain, Middle Aged, Magnetic Resonance Imaging, Brain Disorders, Mental Health, Networking and Information Technology R&D (NITRD), Differential, Biomedical Imaging, Female, Algorithms
Abstract

Automated analysis of MRI data of the subregions of the hippocampus requires computational atlases built at a higher resolution than those that are typically used in current neuroimaging studies. Here we describe the construction of a statistical atlas of the hippocampal formation at the subregion level using ultra-high resolution, ex vivo MRI. Fifteen autopsy samples were scanned at 0.13 mm isotropic resolution (on average) using customized hardware. The images were manually segmented into 13 different hippocampal substructures using a protocol specifically designed for this study; precise delineations were made possible by the extraordinary resolution of the scans. In addition to the subregions, manual annotations for neighboring structures (e.g., amygdala, cortex) were obtained from a separate dataset of in vivo, T1-weighted MRI scans of the whole brain (1mm resolution). The manual labels from the in vivo and ex vivo data were combined into a single computational atlas of the hippocampal formation with a novel atlas building algorithm based on Bayesian inference. The resulting atlas can be used to automatically segment the hippocampal subregions in structural MRI images, using an algorithm that can analyze multimodal data and adapt to variations in MRI contrast due to differences in acquisition hardware or pulse sequences. The applicability of the atlas, which we are releasing as part of FreeSurfer (version 6.0), is demonstrated with experiments on three different publicly available datasets with different types of MRI contrast. The results show that the atlas and companion segmentation method: 1) can segment T1 and T2 images, as well as their combination, 2) replicate findings on mild cognitive impairment based on high-resolution T2 data, and 3) can discriminate between Alzheimer's disease subjects and elderly controls with 88% accuracy in standard resolution (1mm) T1 data, significantly outperforming the atlas in FreeSurfer version 5.3 (86% accuracy) and classification based on whole hippocampal volume (82% accuracy).

Published
2015

308. Klotho Is Neuroprotective in the Superoxide Dismutase (SOD1G93A) Mouse Model of ALS.

Author

Zeldich, Ella, Chen, Ci-Di, Boden, Emma, Howat, Bryce, Nasse, Jason S., Zeldich, Dean, Lambert, Anthony G., Yuste, Andrea, Cherry, Jonathan D., Mathias, Rebecca M., Ma, Qicheng, Lau, Nelson C., McKee, Ann C., Hatzipetros, Theo, and Abraham, Carmela R.

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of motor neurons in the brain and spinal cord. ALS neuropathology is associated with increased oxidative stress, excitotoxicity, and inflammation. We and others reported that the anti-aging and cognition-enhancing protein Klotho is a neuroprotective, antioxidative, anti-inflammatory, and promyelinating protein. In mice, its absence leads to an extremely shortened life span and to multiple phenotypes resembling human aging, including motor and hippocampal neurodegeneration and cognitive impairment. In contrast, its overexpression extends life span, enhances cognition, and confers resistance against oxidative stress; it also reduces premature mortality and cognitive and behavioral abnormalities in an animal model for Alzheimer's disease (AD). These pleiotropic beneficial properties of Klotho suggest that Klotho could be a potent therapeutic target for preventing neurodegeneration in ALS. Klotho overexpression in the SOD1 mouse model of ALS resulted in delayed onset and progression of the disease and extended survival that was more prominent in females than in males. Klotho reduced the expression of neuroinflammatory markers and prevented neuronal loss with the more profound effect in the spinal cord than in the motor cortex. The effect of Klotho was accompanied by reduced expression of proinflammatory cytokines and enhanced the expression of antioxidative and promyelinating factors in the motor cortex and spinal cord of Klotho × SOD1 compared to SOD1 mice. Our study provides evidence that increased levels of Klotho alleviate ALS-associated pathology in the SOD1 mouse model and may serve as a basis for developing Klotho-based therapeutic strategies for ALS. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

309. Cortical degeneration in chronic traumatic encephalopathy and Alzheimer's disease neuropathologic change.

Author

Armstrong, Richard A., McKee, Ann C., Stein, Thor D., Alvarez, Victor E., and Cairns, Nigel J.

Subjects
*CHRONIC traumatic encephalopathy, *ALZHEIMER'S disease, *NEUROFIBRILLARY tangles, *SOCIAL degeneration, *CEREBRAL cortex, *CHI-squared test, *DIAGNOSIS, *NEURONS, *RESEARCH funding
Abstract

Objectives: An observational study to compare the laminar distributions in frontal and temporal cortex of the tau-immunoreactive pathologies in chronic traumatic encephalopathy (CTE) and Alzheimer's disease neuropathologic change (ADNC).Patients: Post-mortem material of (1) four cases of CTE without ADNC, (2) seven cases of CTE with ADNC (CTE/ADNC), and (3) seven cases of ADNC alone.Results: In CTE and CTE/ADNC, neurofibrillary tangles (NFT), neuropil threads (NT), and dot-like grains (DLG) were distributed either in upper cortex or across all layers. Low densities of astrocytic tangles (AT) and abnormally enlarged neurons (EN) were not localized to any specific layer. Surviving neurons exhibited peaks of density in both upper and lower cortex, and vacuole density was greatest in superficial layers. In ADNC, neuritic plaques (NP) were more frequent, AT rare, NFT and NT were more widely distributed, NT affected lower layers more frequently, and surviving neurons were less frequently bimodal than in CTE and CTE/ADNC.Conclusion: Tau pathology in CTE and CTE/ADNC consistently affected the upper cortex but was more widely distributed in ADNC. The presence of CTE may encourage the development of ADNC pathology later in the course of the disease. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

310. Aging-related tau astrogliopathy (ARTAG) : harmonized evaluation strategy

Author

Kovacs, Gabor G., Ferrer, Isidro, Grinberg, Lea T., Alafuzoff, Irina, Attems, Johannes, Budka, Herbert, Cairns, Nigel J., Crary, John F., Duyckaerts, Charles, Ghetti, Bernardino, Halliday, Glenda M., Ironside, James W., Love, Seth, Mackenzie, Ian R., Munoz, David G., Murray, Melissa E., Nelson, Peter T., Takahashi, Hitoshi, Trojanowski, John Q., Ansorge, Olaf, Arzberger, Thomas, Baborie, Atik, Beach, Thomas G., Bieniek, Kevin F., Bigio, Eileen H., Bodi, Istvan, Dugger, Brittany N., Feany, Mel, Gelpi, Ellen, Gentleman, Stephen M., Giaccone, Giorgio, Hatanpaa, Kimmo J., Heale, Richard, Hof, Patrick R., Hofer, Monika, Hortobagyi, Tibor, Jellinger, Kurt, Jicha, Gregory A., Ince, Paul, Kofler, Julia, Koevari, Enikoe, Kril, Jillian J., Mann, David M., Matej, Radoslav, McKee, Ann C., McLean, Catriona, Milenkovic, Ivan, Montine, Thomas J., Murayama, Shigeo, Lee, Edward B., Rahimi, Jasmin, Rodriguez, Roberta D., Rozemuller, Annemieke, Schneider, Julie A., Schultz, Christian, Seeley, William, Seilhean, Danielle, Smith, Colin, Tagliavini, Fabrizio, Takao, Masaki, Thal, Dietmar Rudolf, Toledo, Jon B., Tolnay, Markus, Troncoso, Juan C., Vinters, Harry V., Weis, Serge, Wharton, Stephen B., White, Charles L., III, Wisniewski, Thomas, Woulfe, John M., Yamada, Masahito, Dickson, Dennis W., Kovacs, Gabor G., Ferrer, Isidro, Grinberg, Lea T., Alafuzoff, Irina, Attems, Johannes, Budka, Herbert, Cairns, Nigel J., Crary, John F., Duyckaerts, Charles, Ghetti, Bernardino, Halliday, Glenda M., Ironside, James W., Love, Seth, Mackenzie, Ian R., Munoz, David G., Murray, Melissa E., Nelson, Peter T., Takahashi, Hitoshi, Trojanowski, John Q., Ansorge, Olaf, Arzberger, Thomas, Baborie, Atik, Beach, Thomas G., Bieniek, Kevin F., Bigio, Eileen H., Bodi, Istvan, Dugger, Brittany N., Feany, Mel, Gelpi, Ellen, Gentleman, Stephen M., Giaccone, Giorgio, Hatanpaa, Kimmo J., Heale, Richard, Hof, Patrick R., Hofer, Monika, Hortobagyi, Tibor, Jellinger, Kurt, Jicha, Gregory A., Ince, Paul, Kofler, Julia, Koevari, Enikoe, Kril, Jillian J., Mann, David M., Matej, Radoslav, McKee, Ann C., McLean, Catriona, Milenkovic, Ivan, Montine, Thomas J., Murayama, Shigeo, Lee, Edward B., Rahimi, Jasmin, Rodriguez, Roberta D., Rozemuller, Annemieke, Schneider, Julie A., Schultz, Christian, Seeley, William, Seilhean, Danielle, Smith, Colin, Tagliavini, Fabrizio, Takao, Masaki, Thal, Dietmar Rudolf, Toledo, Jon B., Tolnay, Markus, Troncoso, Juan C., Vinters, Harry V., Weis, Serge, Wharton, Stephen B., White, Charles L., III, Wisniewski, Thomas, Woulfe, John M., Yamada, Masahito, and Dickson, Dennis W.

Abstract

Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astrogli

Published
2016
Full Text
View/download PDF

311. Tau prions from Alzheimer's disease and chronic traumatic encephalopathy patients propagate in cultured cells.

Author

Woerman, Amanda L, Woerman, Amanda L, Aoyagi, Atsushi, Patel, Smita, Kazmi, Sabeen A, Lobach, Iryna, Grinberg, Lea T, McKee, Ann C, Seeley, William W, Olson, Steven H, Prusiner, Stanley B, Woerman, Amanda L, Woerman, Amanda L, Aoyagi, Atsushi, Patel, Smita, Kazmi, Sabeen A, Lobach, Iryna, Grinberg, Lea T, McKee, Ann C, Seeley, William W, Olson, Steven H, and Prusiner, Stanley B

Abstract

Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from deceased individuals with PiD, a neurodegenerative disorder characterized by three-repeat (3R) tau prions, were used to infect HEK293T cells expressing 3R tau fused to yellow fluorescent protein (YFP). Extracts from AGD, CBD, and PSP patient samples, which contain four-repeat (4R) tau prions, were transmitted to HEK293 cells expressing 4R tau fused to YFP. These studies demonstrated that prion propagation in HEK cells requires isoform pairing between the infecting prion and the recipient substrate. Interestingly, tau aggregates in AD and CTE, containing both 3R and 4R isoforms, were unable to robustly infect either 3R- or 4R-expressing cells. However, AD and CTE prions were able to replicate in HEK293T cells expressing both 3R and 4R tau. Unexpectedly, increasing the level of 4R isoform expression alone supported the propagation of both AD and CTE prions. These results allowed us to determine the levels of tau prions in AD and CTE brain extracts.

Published
2016

312. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

Author

Kovacs, Gabor G, Kovacs, Gabor G, Ferrer, Isidro, Grinberg, Lea T, Alafuzoff, Irina, Attems, Johannes, Budka, Herbert, Cairns, Nigel J, Crary, John F, Duyckaerts, Charles, Ghetti, Bernardino, Halliday, Glenda M, Ironside, James W, Love, Seth, Mackenzie, Ian R, Munoz, David G, Murray, Melissa E, Nelson, Peter T, Takahashi, Hitoshi, Trojanowski, John Q, Ansorge, Olaf, Arzberger, Thomas, Baborie, Atik, Beach, Thomas G, Bieniek, Kevin F, Bigio, Eileen H, Bodi, Istvan, Dugger, Brittany N, Feany, Mel, Gelpi, Ellen, Gentleman, Stephen M, Giaccone, Giorgio, Hatanpaa, Kimmo J, Heale, Richard, Hof, Patrick R, Hofer, Monika, Hortobágyi, Tibor, Jellinger, Kurt, Jicha, Gregory A, Ince, Paul, Kofler, Julia, Kövari, Enikö, Kril, Jillian J, Mann, David M, Matej, Radoslav, McKee, Ann C, McLean, Catriona, Milenkovic, Ivan, Montine, Thomas J, Murayama, Shigeo, Lee, Edward B, Rahimi, Jasmin, Rodriguez, Roberta D, Rozemüller, Annemieke, Schneider, Julie A, Schultz, Christian, Seeley, William, Seilhean, Danielle, Smith, Colin, Tagliavini, Fabrizio, Takao, Masaki, Thal, Dietmar Rudolf, Toledo, Jon B, Tolnay, Markus, Troncoso, Juan C, Vinters, Harry V, Weis, Serge, Wharton, Stephen B, White, Charles L, Wisniewski, Thomas, Woulfe, John M, Yamada, Masahito, Dickson, Dennis W, Kovacs, Gabor G, Kovacs, Gabor G, Ferrer, Isidro, Grinberg, Lea T, Alafuzoff, Irina, Attems, Johannes, Budka, Herbert, Cairns, Nigel J, Crary, John F, Duyckaerts, Charles, Ghetti, Bernardino, Halliday, Glenda M, Ironside, James W, Love, Seth, Mackenzie, Ian R, Munoz, David G, Murray, Melissa E, Nelson, Peter T, Takahashi, Hitoshi, Trojanowski, John Q, Ansorge, Olaf, Arzberger, Thomas, Baborie, Atik, Beach, Thomas G, Bieniek, Kevin F, Bigio, Eileen H, Bodi, Istvan, Dugger, Brittany N, Feany, Mel, Gelpi, Ellen, Gentleman, Stephen M, Giaccone, Giorgio, Hatanpaa, Kimmo J, Heale, Richard, Hof, Patrick R, Hofer, Monika, Hortobágyi, Tibor, Jellinger, Kurt, Jicha, Gregory A, Ince, Paul, Kofler, Julia, Kövari, Enikö, Kril, Jillian J, Mann, David M, Matej, Radoslav, McKee, Ann C, McLean, Catriona, Milenkovic, Ivan, Montine, Thomas J, Murayama, Shigeo, Lee, Edward B, Rahimi, Jasmin, Rodriguez, Roberta D, Rozemüller, Annemieke, Schneider, Julie A, Schultz, Christian, Seeley, William, Seilhean, Danielle, Smith, Colin, Tagliavini, Fabrizio, Takao, Masaki, Thal, Dietmar Rudolf, Toledo, Jon B, Tolnay, Markus, Troncoso, Juan C, Vinters, Harry V, Weis, Serge, Wharton, Stephen B, White, Charles L, Wisniewski, Thomas, Woulfe, John M, Yamada, Masahito, and Dickson, Dennis W

Abstract

Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astrogli

Published
2016

314. Osmotic shifts, metabolic compromise, and the vulnerability of the pons

Author

McKee, Ann C.

Subjects
Encephalomyelitis -- Diagnosis, Nervous system diseases -- Diagnosis, Metabolic diseases -- Diagnosis, Health
Abstract

In 1959, Adams, Victor, and Mancall published their landmark article on central pontine myelinolysis, a disease primarily affecting myelinated nerve fibers in the center of the basis pontis and associated [...]

Published
1992

315. Effects of Multiple Genetic Loci on Age at Onset in Late-Onset Alzheimer Disease

Author

Naj, Adam C, Jun, Gyungah, Reitz, Christiane, Kunkle, Brian W, Perry, William, Park, Yo Son, Beecham, Gary W, Rajbhandary, Ruchita A, Hamilton-Nelson, Kara L, Wang, Li-San, Kauwe, John S. K, Huentelman, Matthew J, Myers, Amanda J, Bird, Thomas D, Boeve, Bradley F, Baldwin, Clinton T, Jarvik, Gail P, Crane, Paul K, Rogaeva, Ekaterina, Barmada, M. Michael, Demirci, F. Yesim, Cruchaga, Carlos, Kramer, Patricia L, Ertekin-Taner, Nilufer, Hardy, John, Graff-Radford, Neill R, Green, Robert C, Larson, Eric B, St. George-Hyslop, Peter H, Buxbaum, Joseph D, Evans, Denis A, Schneider, Julie A, Lunetta, Kathryn L, Kamboh, M. Ilyas, Saykin, Andrew J, Reiman, Eric M, De Jager, Philip L, Bennett, David A, Morris, John C, Montine, Thomas J, Goate, Alison M, Blacker, Deborah, Tsuang, Debby W, Hakonarson, Hakon, Kukull, Walter A, Foroud, Tatiana M, Martin, Eden R, Haines, Jonathan L, Mayeux, Richard P, Farrer, Lindsay A, Schellenberg, Gerard D, Pericak-Vance, Margaret A, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Barber, Robert, Barnes, Lisa L, Beach, Thomas G, Becker, James T, Beekly, Duane, Bigio, Eileen H, Bowen, James D, Boxer, Adam, Burke, James R, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlson, Chris S, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cribbs, David H, Crocco, Elizabeth A, DeCarli, Charles, DeKosky, Steven T, Dick, Malcolm, Dickson, Dennis W, Duara, Ranjan, Faber, Kelley M, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Frosch, Matthew P, Galasko, Douglas R, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Glass, Jonathan D, Growdon, John H, Hamilton, Ronald L, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, Hulette, Christine M, Hyman, Bradley T, Jicha, Gregory A, Jin, Lee-Way, Karydas, Anna, Kaye, Jeffrey A, Kim, Ronald, Koo, Edward H, Kowall, Neil W, Kramer, Joel H, LaFerla, Frank M, Lah, James J, Leverenz, James B, Levey, Allan I, Li, Ge, Lieberman, Andrew P, Lin, Chiao-Feng, Lopez, Oscar L, Lyketsos, Constantine G, Mack, Wendy J, Martiniuk, Frank, Mash, Deborah C, Masliah, Eliezer, McCormick, Wayne C, McCurry, Susan M, McDavid, Andrew N, McKee, Ann C, Mesulam, Marsel, Miller, Bruce L, Miller, Carol A, Miller, Joshua W, Murrell, Jill R, Olichney, John M, Pankratz, Vernon S, Parisi, Joseph E, Paulson, Henry L, Peskind, Elaine, Petersen, Ronald C, Pierce, Aimee, Poon, Wayne W, Potter, Huntington, Quinn, Joseph F, Raj, Ashok, Raskind, Murray, Reisberg, Barry, Ringman, John M, Roberson, Erik D, Rosen, Howard J, Rosenberg, Roger N, Sano, Mary, Schneider, Lon S, Seeley, William W, Smith, Amanda G, Sonnen, Joshua A, Spina, Salvatore, Stern, Robert A, Tanzi, Rudolph E, Thornton-Wells, Tricia A, Trojanowski, John Q, Troncoso, Juan C, Valladares, Otto, Van Deerlin, Vivianna M, Van Eldik, Linda J, Vardarajan, Badri N, Vinters, Harry V, Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A, Williamson, Jennifer, Wishnek, Sarah, Woltjer, Randall L, Wright, Clinton B, Younkin, Steven G, Yu, Chang-En, and Yu, Lei

Subjects
Medicine and Health Sciences
Published
2014

316. A new flortaucipir PET biomarker based on graph theory for early detection of CTE in former American football players.

Author

Protas, Hillary D., Su, Yi, Luo, Ji, Chen, Kewei, Alosco, Michael L, Adler, Charles, Balcer, Laura, Bernick, Charles B., Au, Rhoda, Banks, Sarah J, Barr, William, Coleman, Michael J, Dodick, David W., Katz, Douglas I, Marek, Ken, Mariani, Megan, McClean, Michael D, McKee, Ann C., Mez, Jesse B., and Palmisano, Joseph

Abstract

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is characterized by perivascular foci of phosphorylated tau (p‐tau) notably in the depths of sulci, with varying patterns in the cerebral cortex. Prior studies show elevated flortaucipir (FTP) PET binding in former American professional football players(PRO). However, the association of p‐tau with clinical measures remains unclear using regional FTP SUVR as early signs of CTE related tau pathology. Graph theory (GT) takes advantages of the spatial variability in p‐tau load and allows the integration of regional measures to define GT based measures. Here we examine the GT based measures in two CTE cohorts to evaluate their utility in assessing p‐tau related pathology in CTE. Method: The graph procedure was optimized in FTP PET images in a group of 26 PRO with reported cognitive and/or behavorial symptoms and 30 asymptomatic controls without a history of traumatic brain injury (the DETECT Study) and identified the GT measure, entorhinal tau strength, as the target metric with the best group separation between PRO and controls. The optimized graph procedures were then applied to the DIAGNOSE CTE Research Project dataset (99 former PRO, 51 former college football players [COL], and 52 controls without exposure to repetitive head impacts [CTL]) and we examined entorhinal tau strength's ability to differentiate the exposure groups and relationship to consensus based diagnoses of Traumatic Encephalopathy Syndrome (TES), the clinical syndrome associated with CTE. Result: Entorhinal tau strength was significantly different among the three exposure groups (p=0.0001) similar to regional SUVR measures (Figure 1). Regional SUVR did not differentiate players (PRO+COL) with and without TES, while entorhinal tau strength approached although did not reach significance (Figure 2). Entorhinal tau strength is the only FTP measure that showed significant differences (p=0.006) between those players with cognitive impairment and players without (Figure 3). Conclusion: While there is still considerable overlap in between‐group measurements, GT based entorhinal tau strength, is potentially more sensitive in detecting tau changes in players with and without TES. Additional studies are necessary to clarify the value of this new measure in detecting underlying CTE pathology. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

318. Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy

Author

Cherry, Jonathan D., primary, Tripodis, Yorghos, additional, Alvarez, Victor E., additional, Huber, Bertrand, additional, Kiernan, Patrick T., additional, Daneshvar, Daniel H., additional, Mez, Jesse, additional, Montenigro, Philip H., additional, Solomon, Todd M., additional, Alosco, Michael L., additional, Stern, Robert A., additional, McKee, Ann C., additional, and Stein, Thor D., additional

Published
2016
Full Text
View/download PDF

320. Progression of tau pathology within cholinergic nucleus basalis neurons in chronic traumatic encephalopathy: A chronic effects of neurotrauma consortium study

Author

Mufson, Elliott J., primary, Perez, Sylvia E., additional, Nadeem, Muhammad, additional, Mahady, Laura, additional, Kanaan, Nicholas M., additional, Abrahamson, Eric E., additional, Ikonomovic, Milos D., additional, Crawford, Fiona, additional, Alvarez, Victor, additional, Stein, Thor, additional, and McKee, Ann C., additional

Published
2016
Full Text
View/download PDF

325. P2-055: Early Chronic Traumatic Encephalopathy in Young Athletes After Concussive Closed-Head Impact Injury and Mouse Model of Impact Concussion

Author

Goldstein, Lee E., primary, Tagge, Chad A., additional, Fisher, Andrew M., additional, Minaeva, Olga, additional, Gaudreau, Amanda, additional, Zhang, Xiao-Lei, additional, Upreti, Chirag, additional, Ericsson, Maria, additional, Wojnarowicz, Mark W., additional, Casey, Noel F., additional, Moncaster, Juliet A., additional, Nowinski, Christopher, additional, Cantu, Robert, additional, Saman, Sudad, additional, Hall, Garth F., additional, Alvarez, Victor E., additional, Kondo, Asami, additional, Anderson, Andy, additional, Veksler, Ronel, additional, Onos, Kristen, additional, Lu, Haiyan, additional, Senatorov, Vlad, additional, Huber, Bertrand R., additional, Stein, Thor D., additional, Tripodis, Yorghos, additional, Kaufer, Daniela, additional, Lu, Kun Ping, additional, Cleveland, Robin O., additional, Howell, Gareth, additional, Friedman, Alon, additional, Ransohoff, Richard, additional, Lamb, Bruce T., additional, Moss, William C., additional, Stanton, Patric K., additional, and McKee, Ann C., additional

Published
2016
Full Text
View/download PDF

327. Assessment of the genetic variance of late-onset Alzheimer's disease

Author

Ridge, Perry G., primary, Hoyt, Kaitlyn B., additional, Boehme, Kevin, additional, Mukherjee, Shubhabrata, additional, Crane, Paul K., additional, Haines, Jonathan L., additional, Mayeux, Richard, additional, Farrer, Lindsay A., additional, Pericak-Vance, Margaret A., additional, Schellenberg, Gerard D., additional, Kauwe, John S.K., additional, Adams, Perrie M., additional, Albert, Marilyn S., additional, Albin, Roger L., additional, Apostolova, Liana G., additional, Arnold, Steven E., additional, Asthana, Sanjay, additional, Atwood, Craig S., additional, Baldwin, Clinton T., additional, Barber, Robert C., additional, Barmada, Michael M., additional, Barnes, Lisa L., additional, Barral, Sandra, additional, Beach, Thomas G., additional, Becker, James T., additional, Beecham, Gary W., additional, Beekly, Duane, additional, Bennett, David A., additional, Bigio, Eileen H., additional, Bird, Thomas D., additional, Blacker, Deborah, additional, Boeve, Bradley F., additional, Bowen, James D., additional, Boxer, Adam, additional, Burke, James R., additional, Burns, Jeffrey M., additional, Buxbaum, Joseph D., additional, Cairns, Nigel J., additional, Cantwell, Laura B., additional, Cao, Chuanhai, additional, Carlson, Chris S., additional, Carlsson, Cynthia M., additional, Carney, Regina M., additional, Carrasquillo, Minerva M., additional, Carroll, Steven L., additional, Chui, Helena C., additional, Clark, David G., additional, Corneveaux, Jason, additional, Cribbs, David H., additional, Crocco, Elizabeth A., additional, Cruchaga, Carlos, additional, De Jager, Philip L., additional, DeCarli, Charles, additional, Demirci, F. Yesim, additional, Dick, Malcolm, additional, Dickson, Dennis W., additional, Doody, Rachelle S., additional, Duara, Ranjan, additional, Ertekin-Taner, Nilufer, additional, Evans, Denis A., additional, Faber, Kelley M., additional, Fairchild, Thomas J., additional, Fallon, Kenneth B., additional, Fardo, David W., additional, Farlow, Martin R., additional, Ferris, Steven, additional, Foroud, Tatiana M., additional, Frosch, Matthew P., additional, Galasko, Douglas R., additional, Gearing, Marla, additional, Geschwind, Daniel H., additional, Ghetti, Bernardino, additional, Gilbert, John R., additional, Goate, Alison M., additional, Graff-Radford, Neill R., additional, Green, Robert C., additional, Growdon, John H., additional, Hakonarson, Hakon, additional, Hamilton, Ronald L., additional, Hamilton-Nelson, Kara L., additional, Hardy, John, additional, Harrell, Lindy E., additional, Honig, Lawrence S., additional, Huebinger, Ryan M., additional, Huentelman, Matthew J., additional, Hulette, Christine M., additional, Hyman, Bradley T., additional, Jarvik, Gail P., additional, Jicha, Gregory A., additional, Jin, Lee-Way, additional, Jun, Gyungah, additional, Kamboh, M. Ilyas, additional, Karydas, Anna, additional, Katz, Mindy J., additional, Kaye, Jeffrey A., additional, Kim, Ronald, additional, Kowall, Neil W., additional, Kramer, Joel H., additional, Kukull, Walter A., additional, Kunkle, Brian W., additional, LaFerla, Frank M., additional, Lah, James J., additional, Larson, Eric B., additional, Leverenz, James B., additional, Levey, Allan I., additional, Li, Ge, additional, Lieberman, Andrew P., additional, Lin, Chiao-Feng, additional, Lipton, Richard B., additional, Lopez, Oscar L., additional, Lunetta, Kathryn L., additional, Lyketsos, Constantine G., additional, Mack, Wendy J., additional, Marson, Daniel C., additional, Martin, Eden R., additional, Martiniuk, Frank, additional, Mash, Deborah C., additional, Masliah, Eliezer, additional, McCormick, Wayne C., additional, McCurry, Susan M., additional, McDavid, Andrew N., additional, McKee, Ann C., additional, Mesulam, Marsel, additional, Miller, Bruce L., additional, Miller, Carol A., additional, Miller, Joshua W., additional, Montine, Thomas J., additional, Morris, John C., additional, Murrell, Jill R., additional, Myers, Amanda J., additional, Naj, Adam C., additional, O'Bryant, Sid, additional, Olichney, John M., additional, Pankratz, Vernon S., additional, Parisi, Joseph E., additional, Partch, Amanda, additional, Paulson, Henry L., additional, Perry, William, additional, Peskind, Elaine, additional, Petersen, Ronald C., additional, Pierce, Aimee, additional, Poon, Wayne W., additional, Potter, Huntington, additional, Quinn, Joseph F., additional, Raj, Ashok, additional, Raskind, Murray, additional, Reiman, Eric M., additional, Reisberg, Barry, additional, Reisch, Joan S., additional, Reitz, Christiane, additional, Ringman, John M., additional, Roberson, Erik D., additional, Rogaeva, Ekaterina, additional, Rosen, Howard J., additional, Rosenberg, Roger N., additional, Royall, Donald R., additional, Sager, Mark A., additional, Sano, Mary, additional, Saykin, Andrew J., additional, Schneider, Julie A., additional, Schneider, Lon S., additional, Seeley, William W., additional, Smith, Amanda G., additional, Sonnen, Joshua A., additional, Spina, Salvatore, additional, St George-Hyslop, Peter, additional, Stern, Robert A., additional, Swerdlow, Russell H., additional, Tanzi, Rudolph E., additional, Thornton-Wells, Tricia A., additional, Trojanowski, John Q., additional, Troncoso, Juan C., additional, Tsuang, Debby W., additional, Valladares, Otto, additional, Van Deerlin, Vivianna M., additional, Van Eldik, Linda J., additional, Vardarajan, Badri N., additional, Vinters, Harry V., additional, Vonsattel, Jean Paul, additional, Wang, Li-San, additional, Weintraub, Sandra, additional, Welsh-Bohmer, Kathleen A., additional, Wendland, Jens R., additional, Wilhelmsen, Kirk C., additional, Williamson, Jennifer, additional, Wingo, Thomas S., additional, Winslow, Ashley R., additional, Wishnek, Sarah, additional, Woltjer, Randall L., additional, Wright, Clinton B., additional, Wu, Chuang-Kuo, additional, Younkin, Steven G., additional, Yu, Chang-En, additional, and Yu, Lei, additional

Published
2016
Full Text
View/download PDF

328. At the interface of sensory and motor dysfunctions and Alzheimer's disease.

Author

Albers, Mark W, Albers, Mark W, Gilmore, Grover C, Kaye, Jeffrey, Murphy, Claire, Wingfield, Arthur, Bennett, David A, Boxer, Adam L, Buchman, Aron S, Cruickshanks, Karen J, Devanand, Davangere P, Duffy, Charles J, Gall, Christine M, Gates, George A, Granholm, Ann-Charlotte, Hensch, Takao, Holtzer, Roee, Hyman, Bradley T, Lin, Frank R, McKee, Ann C, Morris, John C, Petersen, Ronald C, Silbert, Lisa C, Struble, Robert G, Trojanowski, John Q, Verghese, Joe, Wilson, Donald A, Xu, Shunbin, Zhang, Li I, Albers, Mark W, Albers, Mark W, Gilmore, Grover C, Kaye, Jeffrey, Murphy, Claire, Wingfield, Arthur, Bennett, David A, Boxer, Adam L, Buchman, Aron S, Cruickshanks, Karen J, Devanand, Davangere P, Duffy, Charles J, Gall, Christine M, Gates, George A, Granholm, Ann-Charlotte, Hensch, Takao, Holtzer, Roee, Hyman, Bradley T, Lin, Frank R, McKee, Ann C, Morris, John C, Petersen, Ronald C, Silbert, Lisa C, Struble, Robert G, Trojanowski, John Q, Verghese, Joe, Wilson, Donald A, Xu, Shunbin, and Zhang, Li I

Abstract

Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer's disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled "Sensory and Motor Dysfunctions in Aging and AD." The scientific sessions of the workshop focused on age-related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses.

Published
2015

330. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy

Author

Kovacs, Gabor G., primary, Ferrer, Isidro, additional, Grinberg, Lea T., additional, Alafuzoff, Irina, additional, Attems, Johannes, additional, Budka, Herbert, additional, Cairns, Nigel J., additional, Crary, John F., additional, Duyckaerts, Charles, additional, Ghetti, Bernardino, additional, Halliday, Glenda M., additional, Ironside, James W., additional, Love, Seth, additional, Mackenzie, Ian R., additional, Munoz, David G., additional, Murray, Melissa E., additional, Nelson, Peter T., additional, Takahashi, Hitoshi, additional, Trojanowski, John Q., additional, Ansorge, Olaf, additional, Arzberger, Thomas, additional, Baborie, Atik, additional, Beach, Thomas G., additional, Bieniek, Kevin F., additional, Bigio, Eileen H., additional, Bodi, Istvan, additional, Dugger, Brittany N., additional, Feany, Mel, additional, Gelpi, Ellen, additional, Gentleman, Stephen M., additional, Giaccone, Giorgio, additional, Hatanpaa, Kimmo J., additional, Heale, Richard, additional, Hof, Patrick R., additional, Hofer, Monika, additional, Hortobágyi, Tibor, additional, Jellinger, Kurt, additional, Jicha, Gregory A., additional, Ince, Paul, additional, Kofler, Julia, additional, Kövari, Enikö, additional, Kril, Jillian J., additional, Mann, David M., additional, Matej, Radoslav, additional, McKee, Ann C., additional, McLean, Catriona, additional, Milenkovic, Ivan, additional, Montine, Thomas J., additional, Murayama, Shigeo, additional, Lee, Edward B., additional, Rahimi, Jasmin, additional, Rodriguez, Roberta D., additional, Rozemüller, Annemieke, additional, Schneider, Julie A., additional, Schultz, Christian, additional, Seeley, William, additional, Seilhean, Danielle, additional, Smith, Colin, additional, Tagliavini, Fabrizio, additional, Takao, Masaki, additional, Thal, Dietmar Rudolf, additional, Toledo, Jon B., additional, Tolnay, Markus, additional, Troncoso, Juan C., additional, Vinters, Harry V., additional, Weis, Serge, additional, Wharton, Stephen B., additional, White, Charles L., additional, Wisniewski, Thomas, additional, Woulfe, John M., additional, Yamada, Masahito, additional, and Dickson, Dennis W., additional

Published
2015
Full Text
View/download PDF

331. CONCUSSION, MICROVASCULAR INJURY, AND EARLY TAUOPATHY IN YOUNG ATHLETES AFTER IMPACT HEAD INJURY AND AN IMPACT CONCUSSION MOUSE MODEL

Author

Goldstein, Lee, Minaeva, Olga, Fisher, Andrew M., Tagge, Chad A., Moncaster, Juliet A., Gaudreau-Balderrama, Amanda, Zhang, Xiao-Lei, Wojnarowicz, Mark W., Casey, Noel F., Lu, Haiyan, Kokiko-Cochran, Olga, Saman, Sudad, Ericsson, Maria, Onos, Kristen D., Veksler, Ronel, Senatorov, Vlad, Kondo, Asami, Zhou, Xiao, Miry, Omid, Vose, Linnea R., Gopaul, Katisha, Upreti, Chirag, Nowinski, Christopher, Cantu, Robert, Alvarez, Victor E., Hua, Ning, Tripodis, Yorghos, Anderson, Andrew, Howell, Gareth R., Kaufer, Daniela, Hall, Garth F., Lu, Kun Ping, Ransohoff, Richard, Cleveland, Robin O., Kowall, Neil W., Huber, Bertrand R., Stein, Thor D., Lamb, Bruce T., Moss, William C., Friedman, Alon, Stanton, Patric K., and McKee, Ann C.

Published
2018
Full Text
View/download PDF

333. Contributors

Author

Abdolmohammadi, Bobak, Alosco, Michael L., Alvarez, Victor E., Amyot, Franck, Blennow, Kaj, Budson, Andrew E., Cantu, Robert C., Diaz-Arrastia, Ramon, Gennarelli, Thomas A., Goldstein, Lee, Haber, Margalit, Huber, Bertrand R., Kenney, Kimbra, Koerte, Inga K., McKee, Ann C., Mez, Jesse, Moore, Carol, Nowinski, Christopher J., Rowson, Bethany, Rowson, Steven, Shenton, Martha E., Stein, Thor D., and Stern, Robert A.

Published
2018
Full Text
View/download PDF

334. A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology.

Author

Killiany, Ronald J., Alosco, Michael L., Mez, Jesse, Stern, Robert A., McKee, Ann C., Kowall, Neil W., Sugarman, Michael A., Tripodis, Yorghos, Martin, Brett, Palmisano, Joseph N., Stein, Thor D., DeCarli, Charles, Brett, Martin, Au, Rhoda, and Besser, Lilah M.

Subjects
CLINICAL pathology, WHITE matter (Nerve tissue), MAGNETIC resonance imaging, ALZHEIMER'S disease, NEUROLOGICAL disorders, BRAIN diseases, APOLIPOPROTEINS, BRAIN, PSYCHOLOGICAL tests, RESEARCH funding, LOGISTIC regression analysis, DISEASE complications
Abstract

Background: White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been postulated to be a core feature of Alzheimer's disease. Clinicopathological studies are needed to elucidate and confirm this possibility.Objective: This study examined: 1) the association between antemortem WMH and autopsy-confirmed Alzheimer's disease neuropathology (ADNP), 2) the relationship between WMH and dementia in participants with ADNP, and 3) the relationships among cerebrovascular disease, WMH, and ADNP.Methods: The sample included 82 participants from the National Alzheimer's Coordinating Center's Data Sets who had quantitated volume of WMH from antemortem FLAIR MRI and available neuropathological data. The Clinical Dementia Rating (CDR) scale (from MRI visit) operationalized dementia status. ADNP+ was defined by moderate to frequent neuritic plaques and Braak stage III-VI at autopsy. Cerebrovascular disease neuropathology included infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy.Results: 60/82 participants were ADNP+. Greater volume of WMH predicted increased odds for ADNP (p = 0.037). In ADNP+ participants, greater WMH corresponded with increased odds for dementia (CDR≥1; p = 0.038). WMH predicted cerebral amyloid angiopathy, microinfarcts, infarcts, and lacunes (ps < 0.04). ADNP+ participants were more likely to have moderate-severe arteriolosclerosis and cerebral amyloid angiopathy compared to ADNP-participants (ps < 0.04).Conclusions: This study found a direct association between total volume of WMH and increased odds for having ADNP. In patients with Alzheimer's disease, FLAIR MRI WMH may be able to provide key insight into disease severity and progression. The association between WMH and ADNP may be explained by underlying cerebrovascular disease. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

335. SIRT3 deregulation is linked to mitochondrial dysfunction in Alzheimer's disease.

Author

Lee, Junghee, Kim, Yunha, Liu, Tian, Hwang, Yu Jin, Hyeon, Seung Jae, Im, Hyeonjoo, Lee, Kyungeun, Alvarez, Victor E., McKee, Ann C., Um, Soo‐Jong, Hur, Manwook, Mook‐Jung, Inhee, Kowall, Neil W., and Ryu, Hoon

Subjects
ALZHEIMER'S disease, DEMENTIA, MITOCHONDRIAL pathology, HISTONE deacetylase, SIRTUINS
Abstract

Summary: Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD‐dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD. SIRT3 mRNA and protein levels were significantly decreased in AD cerebral cortex, and Ac‐p53 K320 was significantly increased in AD mitochondria. SIRT3 prevented p53‐induced mitochondrial dysfunction and neuronal damage in a deacetylase activity‐dependent manner. Notably, mitochondrially targeted p53 (mito‐p53) directly reduced mitochondria DNA‐encoded ND2 and ND4 gene expression resulting in increased reactive oxygen species (ROS) and reduced mitochondrial oxygen consumption. ND2 and ND4 gene expressions were significantly decreased in patients with AD. p53‐ChIP analysis verified the presence of p53‐binding elements in the human mitochondrial genome and increased p53 occupancy of mitochondrial DNA in AD. SIRT3 overexpression restored the expression of ND2 and ND4 and improved mitochondrial oxygen consumption by repressing mito‐p53 activity. Our results indicate that SIRT3 dysfunction leads to p53‐mediated mitochondrial and neuronal damage in AD. Therapeutic modulation of SIRT3 activity may ameliorate mitochondrial pathology and neurodegeneration in AD. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

336. Dementia After Moderate-Severe Traumatic Brain Injury: Coexistence of Multiple Proteinopathies.

Author

Kenney, Kimbra, Iacono, Diego, Edlow, Brian L., Katz, Douglas I., Diaz-Arrastia, Ramon, Dams-O'Connor, Kristen, Daneshvar, Daniel H., Stevens, Allison, Moreau, Allison L., Tirrell, Lee S., Varjabedian, Ani, Yendiki, Anastasia, Kouwe, Andre van der, Mareyam, Azma, McNab, Jennifer A., Gordon, Wayne A., Fischl, Bruce, McKee, Ann C., and Perl, Daniel P.

Published
2018
Full Text
View/download PDF

338. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W., Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C., Damotte, Vincent, Naj, Adam C., Boland, Anne, Vronskaya, Maria, van der Lee, Sven J., Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R., Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L., Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B., Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N., Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W., Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L., Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V., Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C., Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T., Adams, Hieab H., Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A., Dombroski, Beth A., Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B., Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S., Meslage, Stéphane, Kornhuber, Johannes, White, Charles C., Song, Yuenjoo, Barber, Robert C., Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M., Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L. Adrienne, Albert, Marilyn S., De Deyn, Peter P., Gu, Wei, Himali, Jayanadra J., Beekly, Duane, Squassina, Alessio, Hartmann, Annette M., Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E., Doody, Rachelle S., Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J., Benito, Yolanda A., Holmes, Clive, Karamujić-Čomić, Hata, Frosch, Matthew P., Thonberg, Hakan, Maier, Wolfgang, Roshchupkin, Gennady, Ghetti, Bernardino, Giedraitis, Vilmantas, Kawalia, Amit, Li, Shuo, Huebinger, Ryan M., Kilander, Lena, Moebus, Susanne, Hernández, Isabel, Kamboh, M. Ilyas, Brundin, RoseMarie, Turton, James, Yang, Qiong, Katz, Mindy J., Concari, Letizia, Lord, Jenny, Beiser, Alexa S., Keene, C. Dirk, Helisalmi, Seppo, Kloszewska, Iwona, Kukull, Walter A., Koivisto, Anne Maria, Lynch, Aoibhinn, Tarraga, Lluís, Larson, Eric B., Haapasalo, Annakaisa, Lawlor, Brian, Mosley, Thomas H., Lipton, Richard B., Solfrizzi, Vincenzo, Gill, Michael, Longstreth, W. T., Montine, Thomas J., Frisardi, Vincenza, Diez-Fairen, Monica, Rivadeneira, Fernando, Petersen, Ronald C., Deramecourt, Vincent, Alvarez, Ignacio, Salani, Francesca, Ciaramella, Antonio, Boerwinkle, Eric, Reiman, Eric M., Fievet, Nathalie, Rotter, Jerome I., Reisch, Joan S., Hanon, Olivier, Cupidi, Chiara, Andre Uitterlinden, A. G., Royall, Donald R., Dufouil, Carole, Maletta, Raffaele Giovanni, de Rojas, Itziar, Sano, Mary, Brice, Alexis, Cecchetti, Roberta, George-Hyslop, Peter St, Ritchie, Karen, Tsolaki, Magda, Tsuang, Debby W., Dubois, Bruno, Craig, David, Wu, Chuang-Kuo, Soininen, Hilkka, Avramidou, Despoina, Albin, Roger L., Fratiglioni, Laura, Germanou, Antonia, Apostolova, Liana G., Keller, Lina, Koutroumani, Maria, Arnold, Steven E., Panza, Francesco, Gkatzima, Olymbia, Asthana, Sanjay, Hannequin, Didier, Whitehead, Patrice, Atwood, Craig S., Caffarra, Paolo, Hampel, Harald, Quintela, Inés, Carracedo, Ángel, Lannfelt, Lars, Rubinsztein, David C., Barnes, Lisa L., Pasquier, Florence, Frölich, Lutz, Barral, Sandra, McGuinness, Bernadette, Beach, Thomas G., Johnston, Janet A., Becker, James T., Passmore, Peter, Bigio, Eileen H., Schott, Jonathan M., Bird, Thomas D., Warren, Jason D., Boeve, Bradley F., Lupton, Michelle K., Bowen, James D., Proitsi, Petra, Boxer, Adam, Powell, John F., Burke, James R., Kauwe, John S. K., Burns, Jeffrey M., Mancuso, Michelangelo, Buxbaum, Joseph D., Bonuccelli, Ubaldo, Cairns, Nigel J., McQuillin, Andrew, Cao, Chuanhai, Livingston, Gill, Carlson, Chris S., Bass, Nicholas J., Carlsson, Cynthia M., Hardy, John, Carney, Regina M., Bras, Jose, Carrasquillo, Minerva M., Guerreiro, Rita, Allen, Mariet, Chui, Helena C., Fisher, Elizabeth, Masullo, Carlo, Crocco, Elizabeth A., DeCarli, Charles, Bisceglio, Gina, Dick, Malcolm, Ma, Li, Duara, Ranjan, Graff-Radford, Neill R., Evans, Denis A., Hodges, Angela, Faber, Kelley M., Scherer, Martin, Fallon, Kenneth B., Riemenschneider, Matthias, Fardo, David W., Heun, Reinhard, Farlow, Martin R., Kölsch, Heike, Ferris, Steven, Leber, Markus, Foroud, Tatiana M., Heuser, Isabella, Galasko, Douglas R., Giegling, Ina, Gearing, Marla, Hüll, Michael, Geschwind, Daniel H., Gilbert, John R., Morris, John, Green, Robert C., Mayo, Kevin, Growdon, John H., Feulner, Thomas, Hamilton, Ronald L., Harrell, Lindy E., Drichel, Dmitriy, Honig, Lawrence S., Cushion, Thomas D., Huentelman, Matthew J., Hollingworth, Paul, Hulette, Christine M., Hyman, Bradley T., Marshall, Rachel, Jarvik, Gail P., Meggy, Alun, Abner, Erin, Menzies, Georgina E., Jin, Lee-Way, Leonenko, Ganna, Real, Luis M., Jun, Gyungah R., Baldwin, Clinton T., Grozeva, Detelina, Karydas, Anna, Russo, Giancarlo, Kaye, Jeffrey A., Kim, Ronald, Jessen, Frank, Kowall, Neil W., Vellas, Bruno, Kramer, Joel H., Vardy, Emma, LaFerla, Frank M., Jöckel, Karl-Heinz, Lah, James J., Dichgans, Martin, Leverenz, James B., Mann, David, Levey, Allan I., Pickering-Brown, Stuart, Lieberman, Andrew P., Klopp, Norman, Lunetta, Kathryn L., Wichmann, H-Erich, Lyketsos, Constantine G., Morgan, Kevin, Marson, Daniel C., Brown, Kristelle, Martiniuk, Frank, Medway, Christopher, Mash, Deborah C., Nöthen, Markus M., Masliah, Eliezer, Hooper, Nigel M., McCormick, Wayne C., Daniele, Antonio, McCurry, Susan M., Bayer, Anthony, McDavid, Andrew N., Gallacher, John, McKee, Ann C., van den Bussche, Hendrik, Mesulam, Marsel, Brayne, Carol, Miller, Bruce L., Riedel-Heller, Steffi, Miller, Carol A., Miller, Joshua W., Al-Chalabi, Ammar, Morris, John C., Shaw, Christopher E., Myers, Amanda J., Wiltfang, Jens, O’Bryant, Sid, Olichney, John M., Alvarez, Victoria, Parisi, Joseph E., Singleton, Andrew B., Paulson, Henry L., Collinge, John, Perry, William R., Mead, Simon, Peskind, Elaine, Cribbs, David H., Rossor, Martin, Pierce, Aimee, Ryan, Natalie S., Poon, Wayne W., Nacmias, Benedetta, Potter, Huntington, Sorbi, Sandro, Quinn, Joseph F., Sacchinelli, Eleonora, Raj, Ashok, Spalletta, Gianfranco, Raskind, Murray, Caltagirone, Carlo, Bossù, Paola, Orfei, Maria Donata, Reisberg, Barry, Clarke, Robert, Reitz, Christiane, Smith, A David, Ringman, John M., Warden, Donald, Roberson, Erik D., Wilcock, Gordon, Rogaeva, Ekaterina, Bruni, Amalia Cecilia, Rosen, Howard J., Gallo, Maura, Rosenberg, Roger N., Ben-Shlomo, Yoav, Sager, Mark A., Mecocci, Patrizia, Saykin, Andrew J., Pastor, Pau, Cuccaro, Michael L., Vance, Jeffery M., Schneider, Julie A., Schneider, Lori S., Slifer, Susan, Seeley, William W., Smith, Amanda G., Sonnen, Joshua A., Spina, Salvatore, Stern, Robert A., Swerdlow, Russell H., Tang, Mitchell, Tanzi, Rudolph E., Trojanowski, John Q., Troncoso, Juan C., Van Deerlin, Vivianna M., Van Eldik, Linda J., Vinters, Harry V., Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A., Wilhelmsen, Kirk C., Williamson, Jennifer, Wingo, Thomas S., Woltjer, Randall L., Wright, Clinton B., Yu, Chang-En, Yu, Lei, Saba, Yasaman, Pilotto, Alberto, Bullido, Maria J., Peters, Oliver, Crane, Paul K., Bennett, David, Bosco, Paola, Coto, Eliecer, Boccardi, Virginia, De Jager, Phil L., Lleo, Alberto, Warner, Nick, Lopez, Oscar L., Ingelsson, Martin, Deloukas, Panagiotis, Cruchaga, Carlos, Graff, Caroline, Gwilliam, Rhian, Fornage, Myriam, Goate, Alison M., Sanchez-Juan, Pascual, Kehoe, Patrick G., Amin, Najaf, Ertekin-Taner, Nilifur, Berr, Claudine, Debette, Stéphanie, Love, Seth, Launer, Lenore J., Younkin, Steven G., Dartigues, Jean-Francois, Corcoran, Chris, Ikram, M. Arfan, Dickson, Dennis W., Nicolas, Gael, Campion, Dominique, Tschanz, JoAnn, Schmidt, Helena, Hakonarson, Hakon, Clarimon, Jordi, Munger, Ron, Schmidt, Reinhold, Farrer, Lindsay A., Van Broeckhoven, Christine, C. O’Donovan, Michael, DeStefano, Anita L., Jones, Lesley, Haines, Jonathan L., Deleuze, Jean-Francois, Owen, Michael J., Gudnason, Vilmundur, Mayeux, Richard, Escott-Price, Valentina, Psaty, Bruce M., Ramirez, Alfredo, Wang, Li-San, Ruiz, Agustin, van Duijn, Cornelia M., Holmans, Peter A., Seshadri, Sudha, Williams, Julie, Amouyel, Phillippe, Schellenberg, Gerard D., Lambert, Jean-Charles, and Pericak-Vance, Margaret A.

Abstract

Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1,and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer’s or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer’s disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P= 1.32 × 10−7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

Published
2019
Full Text
View/download PDF

339. American Football Play and Parkinson Disease Among Men.

Author

Bruce, Hannah J., Tripodis, Yorghos, McClean, Michael, Korell, Monica, Tanner, Caroline M., Contreras, Brittany, Gottesman, Joshua, Kirsch, Leslie, Karim, Yasir, Martin, Brett, Palmisano, Joseph, Abdolmohammadi, Bobak, Shih, Ludy C., Stein, Thor D., Stern, Robert A., Adler, Charles H., Mez, Jesse, Nowinski, Chris, McKee, Ann C., and Alosco, Michael L.

Published
2023
Full Text
View/download PDF

340. Prediction of cognitive impairment in morphologically‐ and immunohistochemically‐stained whole slide images reveals white matter alterations.

Author

McKenzie, Andrew T, Marx, Gabriel A., Koenigsberg, Daniel, Sawyer, Mary, Iida, Megan A, Walker, Jamie M., Richardson, Timothy E., Campanella, Gabriele, Attems, Johannes, McKee, Ann C., Stein, Thor D., Fuchs, Thomas J, III, Charles White, Farrell, Kurt W., and Crary, John F.

Abstract

Background: Age‐related cognitive impairment is complex and multifactorial, with numerous underlying and frequently co‐morbid pathological correlates. Given that conventional measures are imperfect predictors of cognitive impairment, improved approaches are urgently needed to identify correlated histopathological changes in an unbiased way. Methods: We used a weakly supervised deep learning algorithm, clustering‐constrained‐attention multiple‐instance learning (CLAM), on digitized whole slide images of human brain tissue sections from a group of elderly individuals without significant amyloid‐beta deposition to predict the presence or absence of cognitive impairment. The brain tissue sections were from the hippocampus and frontal cortex and were either morphologically stained with LH&E or immunohistochemically stained for hyper‐phosphorylated tau. We used attention analysis to pinpoint the underlying architectural and cellular features that the top‐performing models used for the predictions. Results: Despite noisy labels of cognition, our trained models were able to predict the presence of cognitive impairment with an accuracy that significantly beat chance, in both the morphologically stained and immunohistochemically stained whole slide images. Attention‐based analysis of the features most associated with cognitive impairment in both types of whole slide images analyzed suggests that the models identified white matter alterations in donors with cognitive impairment. Conclusions: The deep learning method for the prediction of cognitive impairment that we present, which appears to be minimally influenced by the human‐identified visually salient aspects of whole slide images, may help to discover unexpected aspects of the pathophysiology associated with cognitive impairment in the elderly. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

341. Multiple mechanisms of extracellular tau spreading in a non-transgenic tauopathy model

Author

Le, Meghan N, Kim, Wonhee, Lee, Sangmook, McKee, Ann C, and Hall, Garth F

Subjects
mental disorders, Original Article
Abstract

While the interneuronal propagation of neurofibrillary lesions in Alzheimer's disease and other tauopathies now appears to involve the spreading of tau-associated toxicity, little is known about its mechanism. We characterized the movement of human tau through the brain of a non-transgenic lower vertebrate tauopathy model in which full-length wild type and mutant human tau isoforms were expressed in identified neurons, thus permitting the identification and localization of EC tau sources. We describe two distinct patterns of tau spreading that correspond to tau species that lack (MTBR-) and contain (MTBR+) the tau microtubule-binding region. These patterns illustrate the production, migration and uptake of EC tau and resemble some of the extracellular tau deposits typically seen in human brain after repeated traumatic injury in cases of chronic traumatic encephalopathy (CTE). We propose that misprocessed human tau can spread between CNS neurons via a variety of non-synaptic mechanisms as well as synaptically mediated mechanisms.

Published
2012

342. Assessing clinicopathological correlation in chronic traumatic encephalopathy: rationale and methods for the UNITE study

Author

Mez, Jesse, primary, Solomon, Todd M., additional, Daneshvar, Daniel H., additional, Murphy, Lauren, additional, Kiernan, Patrick T., additional, Montenigro, Philip H., additional, Kriegel, Joshua, additional, Abdolmohammadi, Bobak, additional, Fry, Brian, additional, Babcock, Katharine J., additional, Adams, Jason W., additional, Bourlas, Alexandra P., additional, Papadopoulos, Zachary, additional, McHale, Lisa, additional, Ardaugh, Brent M., additional, Martin, Brett R., additional, Dixon, Diane, additional, Nowinski, Christopher J., additional, Chaisson, Christine, additional, Alvarez, Victor E., additional, Tripodis, Yorghos, additional, Stein, Thor D., additional, Goldstein, Lee E., additional, Katz, Douglas I., additional, Kowall, Neil W., additional, Cantu, Robert C., additional, Stern, Robert A., additional, and McKee, Ann C., additional

Published
2015
Full Text
View/download PDF

343. A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI

Author

Iglesias, Juan Eugenio, primary, Augustinack, Jean C., additional, Nguyen, Khoa, additional, Player, Christopher M., additional, Player, Allison, additional, Wright, Michelle, additional, Roy, Nicole, additional, Frosch, Matthew P., additional, McKee, Ann C., additional, Wald, Lawrence L., additional, Fischl, Bruce, additional, and Van Leemput, Koen, additional

Published
2015
Full Text
View/download PDF

344. Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage

Author

Martinez‐Ramirez, Sergi, primary, Romero, Jose‐Rafael, additional, Shoamanesh, Ashkan, additional, McKee, Ann C., additional, Van Etten, Ellis, additional, Pontes‐Neto, Octavio, additional, Macklin, Eric A., additional, Ayres, Alison, additional, Auriel, Eitan, additional, Himali, Jayandra J., additional, Beiser, Alexa S., additional, DeCarli, Charles, additional, Stein, Thor D., additional, Alvarez, Victor E., additional, Frosch, Matthew P., additional, Rosand, Jonathan, additional, Greenberg, Steven M., additional, Gurol, M. Edip, additional, Seshadri, Sudha, additional, and Viswanathan, Anand, additional

Published
2015
Full Text
View/download PDF

345. Ice Hockey Summit II

Author

Smith, Aynsley M., primary, Stuart, Michael J., additional, Dodick, David W., additional, Roberts, William O., additional, Alford, Patrick W., additional, Ashare, Alan B., additional, Aubrey, Mark, additional, Benson, Brian W., additional, Burke, Chip J., additional, Dick, Randall, additional, Eickhoff, Chad, additional, Emery, Carolyn A., additional, Flashman, Laura A., additional, Gaz, Daniel, additional, Giza, Chris C., additional, Greenwald, Rick M., additional, Herring, Stan, additional, Hoshizaki, T. Blaine, additional, Hudziak, James J., additional, Huston, John, additional, Krause, Dave, additional, LaVoi, Nicole, additional, Leaf, Matt, additional, Leddy, John J., additional, MacPherson, Alison, additional, McKee, Ann C., additional, Mihalik, Jason P., additional, Moessner, Anne M., additional, Montelpare, William J., additional, Putukian, Margot, additional, Schneider, Kathryn J., additional, Szalkowski, Ron, additional, Tabrum, Mark, additional, Whitehead, Jim, additional, and Wiese-Bjornstal, Diane M., additional

Published
2015
Full Text
View/download PDF

347. Rarity of the Alzheimer Disease–ProtectiveAPPA673T Variant in the United States

Author

Wang, Li-San, primary, Naj, Adam C., additional, Graham, Robert R., additional, Crane, Paul K., additional, Kunkle, Brian W., additional, Cruchaga, Carlos, additional, Murcia, Josue D. Gonzalez, additional, Cannon-Albright, Lisa, additional, Baldwin, Clinton T., additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, Kukull, Walter A., additional, Faber, Kelley M., additional, Schupf, Nicole, additional, Norton, Maria C., additional, Tschanz, JoAnn T., additional, Munger, Ronald G., additional, Corcoran, Christopher D., additional, Rogaeva, Ekaterina, additional, Lin, Chiao-Feng, additional, Dombroski, Beth A., additional, Cantwell, Laura B., additional, Partch, Amanda, additional, Valladares, Otto, additional, Hakonarson, Hakon, additional, St George-Hyslop, Peter, additional, Green, Robert C., additional, Goate, Alison M., additional, Foroud, Tatiana M., additional, Carney, Regina M., additional, Larson, Eric B., additional, Behrens, Timothy W., additional, Kauwe, John S. K., additional, Haines, Jonathan L., additional, Farrer, Lindsay A., additional, Pericak-Vance, Margaret A., additional, Mayeux, Richard, additional, Schellenberg, Gerard D., additional, Albert, Marilyn S., additional, Albin, Roger L., additional, Apostolova, Liana G., additional, Arnold, Steven E., additional, Barber, Robert, additional, Barmada, M. Michael, additional, Barnes, Lisa L., additional, Beach, Thomas G., additional, Becker, James T., additional, Beecham, Gary W., additional, Beekly, Duane, additional, Bennett, David A., additional, Bigio, Eileen H., additional, Bird, Thomas D., additional, Blacker, Deborah, additional, Boeve, Bradley F., additional, Bowen, James D., additional, Boxer, Adam, additional, Burke, James R., additional, Buxbaum, Joseph D., additional, Cairns, Nigel J., additional, Cao, Chuanhai, additional, Carlson, Chris S., additional, Carroll, Steven L., additional, Chui, Helena C., additional, Clark, David G., additional, Cribbs, David H., additional, Crocco, Elizabeth A., additional, DeCarli, Charles, additional, DeKosky, Steven T., additional, Demirci, F. Yesim, additional, Dick, Malcolm, additional, Dickson, Dennis W., additional, Duara, Ranjan, additional, Ertekin-Taner, Nilufer, additional, Fallon, Kenneth B., additional, Farlow, Martin R., additional, Ferris, Steven, additional, Frosch, Matthew P., additional, Galasko, Douglas R., additional, Ganguli, Mary, additional, Gearing, Marla, additional, Geschwind, Daniel H., additional, Ghetti, Bernardino, additional, Gilbert, John R., additional, Glass, Jonathan D., additional, Graff-Radford, Neill R., additional, Growdon, John H., additional, Hamilton, Ronald L., additional, Hamilton-Nelson, Kara L., additional, Harrell, Lindy E., additional, Head, Elizabeth, additional, Honig, Lawrence S., additional, Hulette, Christine M., additional, Hyman, Bradley T., additional, Jarvik, Gail P., additional, Jicha, Gregory A., additional, Jin, Lee-Way, additional, Jun, Gyungah, additional, Kamboh, M. Ilyas, additional, Karydas, Anna, additional, Kaye, Jeffrey A., additional, Kim, Ronald, additional, Koo, Edward H., additional, Kowall, Neil W., additional, Kramer, Joel H., additional, Kramer, Patricia, additional, LaFerla, Frank M., additional, Lah, James J., additional, Leverenz, James B., additional, Levey, Allan I., additional, Li, Ge, additional, Lieberman, Andrew P., additional, Lopez, Oscar L., additional, Lunetta, Kathryn L., additional, Lyketsos, Constantine G., additional, Mack, Wendy J., additional, Marson, Daniel C., additional, Martin, Eden R., additional, Martiniuk, Frank, additional, Mash, Deborah C., additional, Masliah, Eliezer, additional, McCormick, Wayne C., additional, McCurry, Susan M., additional, McDavid, Andrew N., additional, McKee, Ann C., additional, Mesulam, M. Marsel, additional, Miller, Bruce L., additional, Miller, Carol A., additional, Miller, Joshua W., additional, Montine, Thomas J., additional, Morris, John C., additional, Murrell, Jill R., additional, Olichney, John M., additional, Parisi, Joseph E., additional, Perry, William, additional, Peskind, Elaine, additional, Petersen, Ronald C., additional, Pierce, Aimee, additional, Poon, Wayne W., additional, Potter, Huntington, additional, Quinn, Joseph F., additional, Raj, Ashok, additional, Raskind, Murray, additional, Reiman, Eric M., additional, Reisberg, Barry, additional, Reitz, Christiane, additional, Ringman, John M., additional, Roberson, Erik D., additional, Rosen, Howard J., additional, Rosenberg, Roger N., additional, Sano, Mary, additional, Saykin, Andrew J., additional, Schneider, Julie A., additional, Schneider, Lon S., additional, Seeley, William W., additional, Smith, Amanda G., additional, Sonnen, Joshua A., additional, Spina, Salvatore, additional, Stern, Robert A., additional, Tanzi, Rudolph E., additional, Thornton-Wells, Tricia A., additional, Trojanowski, John Q., additional, Troncoso, Juan C., additional, Tsuang, Debby W., additional, Van Deerlin, Vivianna M., additional, Van Eldik, Linda J., additional, Vardarajan, Badri N., additional, Vinters, Harry V., additional, Vonsattel, Jean Paul, additional, Weintraub, Sandra, additional, Welsh-Bohmer, Kathleen A., additional, Williamson, Jennifer, additional, Wishnek, Sarah, additional, Woltjer, Randall L., additional, Wright, Clinton B., additional, Younkin, Steven G., additional, Yu, Chang-En, additional, and Yu, Lei, additional

Published
2015
Full Text
View/download PDF

348. Self-reported concussion history: impact of providing a definition of concussion.

Author

Robbins, Clifford A, Robbins, Clifford A, Daneshvar, Daniel H, Picano, John D, Gavett, Brandon E, Baugh, Christine M, Riley, David O, Nowinski, Christopher J, McKee, Ann C, Cantu, Robert C, Stern, Robert A, Robbins, Clifford A, Robbins, Clifford A, Daneshvar, Daniel H, Picano, John D, Gavett, Brandon E, Baugh, Christine M, Riley, David O, Nowinski, Christopher J, McKee, Ann C, Cantu, Robert C, and Stern, Robert A

Abstract

BackgroundIn recent years, the understanding of concussion has evolved in the research and medical communities to include more subtle and transient symptoms. The accepted definition of concussion in these communities has reflected this change. However, it is unclear whether this shift is also reflected in the understanding of the athletic community.What is known about the subjectSelf-reported concussion history is an inaccurate assessment of someone's lifetime exposure to concussive brain trauma. However, unfortunately, in many cases it is the only available tool.Hypothesis/purposeWe hypothesize that athletes' self-reported concussion histories will be significantly greater after reading them the current definition of concussion, relative to the reporting when no definition was provided. An increase from baseline to post-definition response will suggest that athletes are unaware of the currently accepted medical definition.Study designCross-sectional study of 472 current and former athletes.MethodsInvestigators conducted structured telephone interviews with current and former athletes between January 2010 and January 2013, asking participants to report how many concussions they had received in their lives. Interviewers then read participants a current definition of concussion, and asked them to re-estimate based on that definition.ResultsTHE TWO ESTIMATES WERE SIGNIFICANTLY DIFFERENT (WILCOXON SIGNED RANK TEST: z=15.636, P<0.001). Comparison of the baseline and post-definition medians (7 and 15, respectively) indicated that the post-definition estimate was approximately twice the baseline. Follow-up analyses indicated that this effect was consistent across all levels of competition examined and across type of sport (contact versus non-contact).ConclusionOur results indicate that athletes' current understandings of concussions are not consistent with a currently accepted medical definition. We strongly recommend that clinicians and researchers preface requests for

Published
2014

349. Self-reported concussion history: impact of providing a definition of concussion

Author

Robbins,Clifford A, Daneshvar,Daniel H, Picano,John D, Gavett,Brandon E, Baugh,Christine M, Riley,David O, Nowinski,Christopher K, McKee,Ann C, Cantu,Robert C, Stern,Robert A, Robbins,Clifford A, Daneshvar,Daniel H, Picano,John D, Gavett,Brandon E, Baugh,Christine M, Riley,David O, Nowinski,Christopher K, McKee,Ann C, Cantu,Robert C, and Stern,Robert A

Abstract

Clifford A Robbins,1 Daniel H Daneshvar,1,2 John D Picano,1,3 Brandon E Gavett,1,4 Christine M Baugh,1,2 David O Riley,1 Christopher J Nowinski,1,2,5 Ann C McKee,1,2,6–8 Robert C Cantu,1,5,9,10 Robert A Stern1,2,8,91Center for the Study of Traumatic Encephalopathy, 2Department of Neurology, Boston University School of Medicine, Boston, MA, USA; 3School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY, USA; 4Department of Psychology, University of Colorado, Colorado Springs, CO, USA; 5Sports Legacy Institute, Waltham MA, USA; 6United States Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA, USA; 7Department of Pathology, 8Alzheimer's Disease Center, 9Department of Neurosurgery, Boston University School of Medicine, Boston, MA, USA; 10Department of Neurosurgery, Emerson Hospital, Concord, MA, USABackground: In recent years, the understanding of concussion has evolved in the research and medical communities to include more subtle and transient symptoms. The accepted definition of concussion in these communities has reflected this change. However, it is unclear whether this shift is also reflected in the understanding of the athletic community.What is known about the subject: Self-reported concussion history is an inaccurate assessment of someone's lifetime exposure to concussive brain trauma. However, unfortunately, in many cases it is the only available tool.Hypothesis/purpose: We hypothesize that athletes' self-reported concussion histories will be significantly greater after reading them the current definition of concussion, relative to the reporting when no definition was provided. An increase from baseline to post-definition response will suggest that athletes are unaware of the currently accepted medical definition.Study design: Cross-sectional study of 472 current and former athletes.Methods: Investigators conducted structured telephone interviews with current and former athletes betw

Published
2014

350. CONCUSSION, MICROVASCULAR INJURY, AND EARLY TAUOPATHY IN YOUNG ATHLETES AFTER IMPACT HEAD INJURY AND AN IMPACT CONCUSSION MOUSE MODE

Author

Fisher, Andrew M., Tagge, Chad A., Minaeva, Olga, Gaudreau, Amanda, Moncaster, Juliet A., Zhang, Xiao-Lei, Wojnarowicz, Mark W., Casey, Noel F., Lu, Haiyan, Kokiko-Cochran, Olga, Saman, Sudad, Ericsson, Maria, Onos, Kristen, Veksler, Ronel, Senatorov, Vlad, Kondo, Asami, Zhou, Xiao, Miry, Omid, Vose, Linnea R., Gopaul, Katisha, Upreti, Chirag, Nowinski, Christopher, Cantu, Robert, Alvarez, Victor E., Hua, Ning, Tripodis, Yorghos, Anderson, Andrew, Howell, Gareth, Kaufer, Daniela, Hall, Garth F., Lu, Kun Ping, Ransohoff, Richard, Cleveland, Robin O., Kowall, Neil W., Huber, Bertrand R., Stein, Thor D., Lamb, Bruce T., Moss, William C., Friedman, Alon, Stanton, Patric K., McKee, Ann C., and Goldstein, Lee E.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results