Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho - Campus de Gualtar, Braga, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Adv Exp Med Biol. 2019;1184:241-257. doi: 10.1007/978-981-32-9358-8_20.
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with a complex physiopathology whose initiators are poorly defined. Accumulating clinical and experimental evidence suggests a causal role of lifetime stress in AD. This chapter summarizes current knowledge about how chronic stress and its accompanying high levels of glucocorticoid (GC) secretion, trigger the two main pathomechanisms of AD: (i) misprocessing of amyloid precursor protein (APP) and the generation of amyloid beta (Aβ) and (ii) Tau hyperphosphorylation and aggregation. Given that depression is a well-known stress-related illness, and the evidence that depression may precede AD, this chapter also explores neurobiological mechanisms that may be common to depressive and AD pathologies. This review also discusses emerging insights into the role of Tau and its malfunction in disrupting neuronal cascades and neuroplasticity and, thus triggering brain pathology.
阿尔茨海默病（AD）是一种多因素神经退行性疾病，其病理生理学十分复杂，其发病因素尚不清楚。越来越多的临床和实验证据表明，终生压力在 AD 中起因果作用。本章总结了目前关于慢性压力及其伴随的高水平糖皮质激素（GC）分泌如何触发 AD 的两个主要发病机制的知识：（i）淀粉样前体蛋白（APP）的错误处理和淀粉样β（Aβ）的产生，以及（ii）Tau 的过度磷酸化和聚集。鉴于抑郁症是一种众所周知的与压力相关的疾病，而且有证据表明抑郁症可能先于 AD 发生，本章还探讨了可能与抑郁和 AD 病理学共有的神经生物学机制。本综述还讨论了 Tau 的作用及其在破坏神经元级联和神经可塑性方面的功能障碍的新见解，从而引发了大脑病理学。
