可溶性AB42寡聚体的LTP抑制作用 200 (Injected into ventricles 10 min before high frequency stimulation of 180 the rat Schaffer collateral pathway). 160 CM ="conditioned medium"from a cell line engineered to express AB 140 Wild Type CM 12 100 Soluble Oligomers of AB42 80 CM+Aβoligomers AB42多肽形成~4-40可溶性寡聚体 与其它蛋白质结合或形成淀粉样斑块， 200 180 AB42(containing ~12 to 40 160 peptides)对神经元的毒性， 12 CM Antibody against AB 12-聚体的毒性作用最强 100 CM+nonspecific 80 “control'"antibody 40 80 120 160 200 AHFS Time(min)
(Injected into ventricles 10 min before high frequency stimulation of the rat Schaffer collateral pathway). CM = “conditioned medium” from a cell line engineered to express Aβ 可溶性Aβ42 寡聚体的LTP抑制作用 Wild Type CM CM + Aβ oligomers CM + nonspecific “control” antibody CM + Antibody against Aβ Soluble Oligomers of Aβ42 Aβ42 多肽形成 ~4-40可溶性 寡聚体. 与其它蛋白质结合或形成淀粉样斑块. Aβ42 (containing ~12 to 40 peptides) 对神经元的毒性. 12-聚体的毒性作用最强
APP or presinilin,家族性AD DOMINANTLY INHERITED NONDOMINANT FORMS OF AD FORMS OF AD (Including“Sporadic”AD) Missense mutations in the APP or Failure of AB clearance mechanisms Presenilin 1 or 2 genes (e.g.,inheritance of ApoE4,faulty AB degradation,etc.) Increased AB42 production throughout life Gradually rising AB levels with age 2 Accumulation and oligomerization of AB42 in limbic and association cortices 散发性AD与AB的清除有关 ↓ Subtle effects of AB42 oligomers on synaptic efficacy 女 Gradual deposition of AB42 oligomers as diffuse plaques 女 Microglial and astrocytic activation and attendant inflammatory responses Altered neuronal ionic homeostasis;oxidative injury Altered kinase/phosphatase activities lead to tangles Widespread neuronal/synaptic dysfunction and selective neuronal loss, with attendant neurotransmitter deficits DEMENTIA
APP or presinilin → 家族性AD 散发性AD 与Aβ的清除有关