神经系统退行性疾病基础.ppt

What Is Alzheimer Disease ? Alzheimer Disease Growth in U.S. Population Aged 65+, 75+, and 85+ Genes Associated with Alzheimer Disease Classification of Senile Dementia DSM-IV分类 1.阿尔茨海默病 (AD) 2.血管性痴呆 (CVD) 3.脑外伤所致痴呆 4.Parkinson病所致痴呆 5.Huntington病所致痴呆 6.HIV病所致痴呆 7.Pick病所致痴呆 8.Creutzfeldt-Jacob病所致痴呆 9.物质和躯体病所致痴呆 10.其它痴呆(Lewy body dementia) AD clinical symptom 认知性症状 Sulfo-glycosaminoglycan content affects PHF-tau solubility and allows the identification of different types of PHFs PS1 may act as a molecular tether, connecting GSK-3? with important substrates. Effects of GSK-3b on AD History of passive antibody therapy In the early 1890s, Behring and Kitasato found that injecting nonlethal doses of tetanus toxin into animals causes the animals blood to develop the ability to neutralize the toxin Inflammation and immune mechanisms in Alzheimer’s disease Adaptive Immunity Microglia lacking E prostanoid receptor subtype 2 have enhanced Ab phagocytosis yet lack Ab-activated neurotoxicity Microglia can be neuroprotective by phagocytosing Ab; however, this comes at the cost of activated innate immunity that causes paracrine damage to neurons. Ablation of E prostanoid receptor subtype 2 significantly increased microglial-mediated clearance of Ab peptides from AD brain sections and suppressed Ab-activated microglia-mediated paracrine neurotoxicity. I would like to talk by a flow of the following contents from now on. I would like to talk by a flow of the following contents from now on. Braak and Braak studies might provide the answer for this question, They counted the number of each stage of Ab deposition and NFT formation at various age. I calculated , using their raw data, and plotted here. Formation of NFTs in entorhinal cortex precede Ab deposition and NFTs in disease state follows by Ab deposition, suggesting that there may be two mechanisms of NFTs formation. One is Ab independent and the other is Ab dependent mechanism. I would like to talk by a flow