Enhanced neurofibrillary tangle formation, cerebral atrophy, and cognitive deficits induced by repetitive mild brain injury in a transgenic tauopathy mouse model.
Traumatic brain injury (TBI) is a risk factors for Alzheimer's disease (AD), and repetitive TBI (rTBI) may culminate in dementia pugilistica (DP), a syndrome characterized by progressive dementia, parkinsonism, and the hallmark brain lesions of AD, including neurofibrillary tangles (NFTs), formed by abnormal tau filaments and senile plaques (SPs) composed of Abeta fibrils. Previous study showed that mild rTBI (mrTBI) accelerated the deposition of Abeta in the brains of transgenic (Tg) mice (Tg2576) that over-express human Abeta precursor proteins with the familial AD Swedish mutations (APP695swe) and model of AD-like amyloidosis. Here, we report studies of the effects of mrTBI on AD-like tau pathologies in Tg mice expressing the shortest human tau isoform (T44) subjected to mrTBI, causing brain concussion without structural brain damage to simulate injuries linked to DP. Twelve-month-old Tg T44 (n = 18) and wild-type (WT; n = 24) mice were subjected to mrTBI (four times a day, 1 day per week, for 4 weeks; n = 24) or sham treatment (n = 18). Histopathological analysis of mice at 9 months after mrTBI revealed that one of the Tg T44 mice showed extensive telencephalic NFT and cerebral atrophy. Although statistical analysis of neurobehavioral tests at 6 months after mrTBI did not show any significant difference in any of groups of mice, the Tg T44 mouse with extensive NFT had an exceptionally low neurobehavioral score. The reasons for the augmentation of tau pathologies in only one T44 tau Tg mouse subjected to mrTBI remain to be elucidated.
Yoshiyama
Yasumasa
Y
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA.
Uryu
Kunihiro
K
Higuchi
Makoto
M
Longhi
Luca
L
Hoover
Rachel
R
Fujimoto
Scott
S
McIntosh
Tracy
T
Lee
Virginia M-Y
VM
Trojanowski
John Q
JQ
D000818:Animals; D001284:Atrophy; D015153:Blotting, Western; D001930:Brain Injuries / Q000150:complications / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000473:pathology*; D024801:Tauopathies / Q000150:complications / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D016875:tau Proteins