Distinct Temporal and Anatomical Distributions of Amyloid-beta and Tau Abnormalities following Controlled Cortical Impact in Transgenic Mice

作者：Tran Hien T^*; Sanchez Laura; Esparza Thomas J; Brody David L

来源：PLos One, 2011, 6(9): e25475.

DOI：10.1371/journal.pone.0025475

Traumatic brain injury TBI is a major environmental risk factor for Alzheimer's disease. Intracellular accumulations of amyloid-beta and tau proteins have been observed within hours following severe TBI in humans. Similar abnormalities have been recapitulated in young 3xTg-AD mice subjected to the controlled cortical impact model (CCI) of TBI and sacrificed at 24 h and 7 days post injury. This study investigated the temporal and anatomical distributions of amyloid-beta and tau abnormalities from 1 h to 24 h post injury in the same model. Intra-axonal amyloid-beta accumulation in the fimbria was detected as early as 1 hour and increased monotonically over 24 hours following injury. Tau immunoreactivity in the fimbria and amygdala had a biphasic time course with peaks at 1 hour and 24 hours, while tau immunoreactivity in the contralateral CA1 rose in a delayed fashion starting at 12 hours after Injury Furthermore, rapid intra-axonal amyloid-beta accumulation was similarly observed post controlled cortical injury in APP/PS1 mice, another transgenic Alzheimer's disease mouse model. Acute increases in total and phospho-tau imunoreactivity were also evident in single transgenic Tau(p301L) mice subjected to controlled cortical injury. These data provide further evidence for the causal effects of moderately severe contusional TBI on acceleration of acute Alzheimer-related abnormalities and the independent la on hip between a amyloid-beta and tau in this setting.

• 出版日期2011-9-29