Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, USA.
J Alzheimers Dis. 2010;20(2):395-408. doi: 10.3233/JAD-2010-1388.
Alzheimer's disease (AD) is a devastating age-related neurodegenerative disorder characterized by progressive impairment of cognition and short-term memory loss. The deposition of amyloid-beta (Abeta) 1-42 into senile plaques is an established feature of AD neuropathology. Controversy still exists about the amyloid pathway as the initiating mechanism or a mere consequence of the events leading to AD. Nevertheless, Abeta toxicity has been probed in vitro and in vivo and increased production or decreased clearance of Abeta peptides are reported to play a major role in the development of AD. Treatment of neural stem cells with Abeta in vitro induces neuronal differentiation. Increased neurogenesis has been also described in AD patients as well as in amyloid-beta protein precursor (AbetaPP) transgenic mice. Adult neurogenesis is greatly enhanced in young AbetaPP transgenic mice, before other AD-liked pathologies, and reduced in older animals. This increased neurogenesis at young ages might be the first pathology related to AD, which is detectable long before other harmful manifestation of the disease. Therefore, understanding the mechanisms of Abeta-induced neurogenesis will reveal insights into the pathogenesis of AD and may prove useful as an early AD biomarker.
阿尔茨海默病（AD）是一种破坏性的与年龄相关的神经退行性疾病，其特征是认知能力逐渐下降和短期记忆丧失。淀粉样蛋白-β（Abeta）1-42 沉积到老年斑中是 AD 神经病理学的一个既定特征。尽管 Abeta 毒性已经在体外和体内进行了研究，但 Abeta 通路是 AD 发病机制的启动机制还是导致 AD 的事件的单纯后果仍存在争议。然而，Abeta 肽的产生增加或清除减少被报道在 AD 的发展中起主要作用。体外用 Abeta 处理神经干细胞可诱导神经元分化。AD 患者以及淀粉样前体蛋白（AbetaPP）转基因小鼠中也描述了神经发生增加。在其他 AD 样病理发生之前，年轻的 AbetaPP 转基因小鼠中的成年神经发生大大增强，而在老年动物中则减少。这种在年轻时增加的神经发生可能是与 AD 相关的最早的病理学改变，在疾病的其他有害表现之前很久就可以检测到。因此，了解 Abeta 诱导的神经发生的机制将揭示 AD 的发病机制，并可能作为 AD 的早期生物标志物证明有用。
