Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer's disease.
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.
Schmidt
M L
ML
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.
Zhukareva
V
V
Newell
K L
KL
Lee
V M
VM
Trojanowski
J Q
JQ
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001265:Athletic Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015153:Blotting, Western; D001914:Boxing / Q000293:injuries*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002490:Central Nervous System / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D000939:Epitopes; D020033:Protein Isoforms; D016875:tau Proteins