| dc.description.abstract | For years, the prevailing hypothesis in Alzheimer's Disease (AD) has proposed a unified mechanism where deposition of amyloid-beta in the brain induces stress responses that lead to tau-pathologies and ultimately cognitive decline. However, despite extensive research on the disease, the exact mechanism of its onset remains unknown. Previous research in our lab has shown that imatinib-methanesulfonate (IM) lowers the amount of central A-beta and rescues cognitive function following a bout of inflammation. The present study aims to expand our understanding of how IM affects AD pathology and further examine the link between A-beta and tau. We hypothesized that prior and co-administration of IM with lipopolysaccharide (LPS) would eliminate elevations in hyperphosphorylated tau (ptau) by reducing production of A-beta. Our results showed that, despite its poor ability to penetrate the blood brain barrier, peripheral treatment with IM reduces levels of central ptau even in the presence of LPS-induced inflammation. Furthermore, total tau was significantly decreased following fourteen consecutive days of IM administration. These results lead us to propose that the expression of tau following LPS administration may be a protective measure by hippocampal neurons to compensate for the loss of the microtubule-stabilizing protein due to phosphorylation. | |
