Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland.
Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland.
Ageing Res Rev. 2021 Sep;70:101397. doi: 10.1016/j.arr.2021.101397. Epub 2021 Jun 30.
An excess of saturated fatty acids and simple sugars in the diet is a known environmental risk factor of Alzheimer's disease (AD) but the holistic view of the interacting processes through which such diet may contribute to AD pathogenesis is missing. We addressed this need through extensive analysis of published studies investigating the effects of western diet (WD) on AD development in humans and laboratory animals. We reviewed WD-induced systemic alterations comprising metabolic changes, induction of obesity and adipose tissue inflammation, gut microbiota dysbiosis and acceleration of systemic low-grade inflammation. Next we provide an overview of the evidence demonstrating that WD-associated systemic alterations drive impairment of the blood-brain barrier (BBB) and development of neuroinflammation paralleled by accumulation of toxic amyloid. Later these changes are followed by dysfunction of synaptic transmission, neurodegeneration and finally memory and cognitive impairment. We conclude that WD can trigger AD by acceleration of inflammaging, and that BBB impairment induced by metabolic and systemic inflammation play the central role in this process. Moreover, the concurrence of neuroinflammation and Aβ dyshomeostasis, which by reciprocal interactions drive the vicious cycle of neurodegeneration, contradicts Aβ as the primary trigger of AD. Given that in 2019 the World Health Organization recommended focusing on modifiable risk factors in AD prevention, this overview of the sequential, complex pathomechanisms initiated by WD, which can lead from peripheral disturbances to neurodegeneration, can support future prevention strategies.
饮食中饱和脂肪酸和简单糖过量是已知的阿尔茨海默病（AD）的环境风险因素，但这种饮食如何导致 AD 发病机制的相互作用过程的整体观点尚不清楚。我们通过广泛分析研究西方饮食（WD）对人类和实验室动物 AD 发展影响的已发表研究来满足这一需求。我们回顾了 WD 诱导的全身改变，包括代谢变化、肥胖和脂肪组织炎症的诱导、肠道微生物失调和全身低度炎症的加速。接下来，我们概述了证明 WD 相关全身改变导致血脑屏障（BBB）损伤和神经炎症发展的证据，同时伴有毒性淀粉样蛋白的积累。随后这些变化会导致突触传递功能障碍、神经退行性变，最终导致记忆和认知障碍。我们得出结论，WD 可以通过加速炎症衰老来引发 AD，代谢和全身炎症引起的 BBB 损伤在这个过程中起着核心作用。此外，神经炎症和 Aβ 稳态失调的同时发生，通过相互作用驱动神经退行性变的恶性循环，这与 Aβ 作为 AD 的主要触发因素相矛盾。鉴于 2019 年世界卫生组织建议专注于 AD 预防的可改变风险因素，因此，WD 引发的这种连续、复杂的发病机制概述，从外周紊乱到神经退行性变，可以为未来的预防策略提供支持。
