Journal ArticleDOI
Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer's disease
TLDR
Comparison of tau pathologies in DP with those in AD showed that the same tau epitopes map to filamentous tau inclusions in AD and DP brains, while the abnormal tau proteins isolated from DP brains are indistinguishable from the six abnormally phosphorylated brain tau isoforms in AD brains, suggesting recurrent TBI may cause dementia pugilistica by activating pathological mechanisms similar to those involved in AD.Abstract:
Insights into mechanisms of familial Alzheimer's disease (AD) caused by genetic mutations have emerged rapidly compared to sporadic AD. Indeed, despite identification of several sporadic AD risk factors, it remains enigmatic how or why they predispose to neurodegenerative disease. For example, traumatic brain injury (TBI) predisposes to AD, and recurrent TBI in career boxers may cause a progressive memory disorder associated with AD-like brain pathology known as dementia pugilistica (DP). Although the reasons for this are unknown, repeated TBI may cause DP by mechanisms similar to those involved in AD. To investigate this possibility, we compared the molecular profile of tau pathologies in DP with those in AD and showed that the same tau epitopes map to filamentous tau inclusions in AD and DP brains, while the abnormal tau proteins isolated from DP brains are indistinguishable from the six abnormally phosphorylated brain tau isoforms in AD brains. Thus, these data suggest that recurrent TBI may cause DP by activating pathological mechanisms similar to those that cause brain degeneration due to accumulations of filamentous tau lesions in AD, and similar, albeit attenuated, activation of these processes by a single TBI may increase susceptibility to sporadic AD decades after the event.read more
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National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease
Bradley T. Hyman,Creighton H. Phelps,Thomas G. Beach,Eileen H. Bigio,Nigel J. Cairns,Maria C. Carrillo,Dennis W. Dickson,Charles Duyckaerts,Matthew P. Frosch,Eliezer Masliah,Suzanne S. Mirra,Peter T. Nelson,Julie A. Schneider,Dietmar Rudolf Thal,Bill Thies,John Q. Trojanowski,Harry V. Vinters,Thomas J. Montine +17 more
TL;DR: The new guidelines recognize the pre‐clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, and establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP‐43 inclusions.
Journal ArticleDOI
Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury.
Ann C. McKee,Robert C. Cantu,Christopher J. Nowinski,E. Tessa Hedley-Whyte,Brandon E. Gavett,Andrew E. Budson,Veronica Santini,H. J. Lee,Caroline A. Kubilus,Robert S. Stern +9 more
TL;DR: This work reviews 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 professionalathletes, 1 football player and 2 boxers.
Journal ArticleDOI
National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach
Thomas J. Montine,Creighton H. Phelps,Thomas G. Beach,Eileen H. Bigio,Nigel J. Cairns,Dennis W. Dickson,Charles Duyckaerts,Matthew P. Frosch,Eliezer Masliah,Suzanne S. Mirra,Peter T. Nelson,Julie A. Schneider,Dietmar Rudolf Thal,John Q. Trojanowski,Harry V. Vinters,Bradley T. Hyman +15 more
TL;DR: A practical guide for the implementation of recently revised National Institute on Aging–Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer’s disease is presented.
Journal ArticleDOI
The spectrum of disease in chronic traumatic encephalopathy
Ann C. McKee,Thor D. Stein,Thor D. Stein,Christopher J. Nowinski,Robert S. Stern,Daniel H. Daneshvar,Victor E. Alvarez,H. J. Lee,Garth F. Hall,Sydney M. Wojtowicz,Sydney M. Wojtowicz,Christine M. Baugh,David O. Riley,Caroline A. Kubilus,Kerry Cormier,Matthew A. Jacobs,Brett Martin,Carmela R. Abraham,Tsuneya Ikezu,Robert Ross Reichard,Benjamin Wolozin,Andrew E. Budson,Andrew E. Budson,Lee E. Goldstein,Neil W. Kowall,Robert C. Cantu +25 more
TL;DR: The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.
Journal ArticleDOI
Pathology of Neurodegenerative Diseases
TL;DR: This review details the human pathology of select neurodegenerative disorders, focusing on their main protein aggregates, and suggests that abnormal protein conformers may spread from cell to cell along anatomically connected pathways.
References
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Journal Article
Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies.
Minami Baba,Shigeo Nakajo,P.-H. Tu,Taisuke Tomita,K. Nakaya,Virginia M.-Y. Lee,John Q. Trojanowski,Takeshi Iwatsubo +7 more
TL;DR: Western blot analyses of highly purified LBs from DLB brains showed that full-length as well as partially truncated and insoluble aggregates of alpha-synuclein are deposited in LBs, which strongly implicate alpha- Synuclein in the formation of LBs and the selective degeneration of neurons in sporadic PD and DLB.
Journal ArticleDOI
A68: a major subunit of paired helical filaments and derivatized forms of normal Tau
TL;DR: The major subunits of a class of PHFs are A68 proteins and the excessive or inappropriate phosphorylation of normal tau may change its apparent Mr, thus transforming tau into A68.
Journal ArticleDOI
Mutation-Specific Functional Impairments in Distinct Tau Isoforms of Hereditary FTDP-17
Ming Hong,Victoria Zhukareva,Vanessa Vogelsberg-Ragaglia,Zbigniew K. Wszolek,Lee Reed,Bruce I. Miller,Daniel H. Geschwind,Thomas D. Bird,Daniel W. McKeel,Alison Goate,John C. Morris,Kirk C. Wilhelmsen,Gerard D. Schellenberg,John Q. Trojanowski,Virginia M.-Y. Lee +14 more
TL;DR: Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in disease pathogenesis by reducing the ability of tau to bind microtubules and promote microtubule assembly.
Journal ArticleDOI
Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding.
Gregory T. Bramblett,Michel Goedert,Ross Jakes,Sandra E. Merrick,John Q. Trojanowski,Virginia M.-Y. Lee +5 more
TL;DR: It is demonstrated that native A68 does not bind to microtubules (MTs), yet dephosphorylated A68 regains the ability to bind to MTs, and phosphorylation of Ser396 may destabilize MTs in AD, resulting in the degeneration of affected cells.
Journal ArticleDOI
Association of apolipoprotein E polymorphism with outcome after head injury
TL;DR: A significant genetic association of APOE polymorphism with outcome after head injury is shown supporting the hypothesis of a genetically determined influence.
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