distinct temporal and anatomical distributions of amyloid-β and tau abnormalities following controlled cortical impact in transgenic mice不同时间和解剖分布amyloid-β和τ异常后控制转基因小鼠大脑皮层的影响.pdfVIP

Distinct Temporal and Anatomical Distributions of Amyloid-b and Tau Abnormalities following Controlled Cortical Impact in Transgenic Mice 1 1 1 1,2 Hien T. Tran , Laura Sanchez , Thomas J. Esparza , David L. Brody * 1 Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, United States of America, 2 Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, Missouri, United States of America Abstract Traumatic brain injury (TBI) is a major environmental risk factor for Alzheimer’s disease. Intracellular accumulations of amyloid-b 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-b and tau abnormalities from 1 h to 24 h post injury in the same model. Intra-axonal amyloid-b 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-b 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 immunoreactivity were also evident in single transgenic TauP301L mi