Department of Medicine, College of Medicine, Majmaah University, Majmaah, Saudi Arabia.
Department of Pharmacology, Toxicology and Medicine, Medical Faculty, College of Medicine, Al-Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq.
Cell Mol Neurobiol. 2023 Oct;43(7):3405-3416. doi: 10.1007/s10571-023-01392-y. Epub 2023 Aug 4.
Hypothyroidism (HPT) HPT could be a risk factor for the development and progression of Alzheimer's disease (AD). In addition, progressive neurodegeneration in AD may affect the metabolism of thyroid hormones (THs) in the brain causing local brain HPT. Hence, the present review aimed to clarify the potential association between HPT and AD. HPT promotes the progression of AD by inducing the production of amyloid beta (Aβ) and tau protein phosphorylation with the development of synaptic plasticity and memory dysfunction. Besides, the metabolism of THs is dysregulated in AD due to the accumulation of Aβ and tau protein phosphorylation leading to local brain HPT. Additionally, HPT can affect AD neuropathology through various mechanistic pathways including dysregulation of transthyretin, oxidative stress, ER stress, autophagy dysfunction mitochondrial dysfunction, and inhibition of brain-derived neurotrophic factor. Taken together there is a potential link between HPT and AD, as HPT adversely impacts AD neuropathology and the reverse is also true.
甲状腺功能减退症（HPT）可能是阿尔茨海默病（AD）发生和进展的危险因素。此外，AD 中的进行性神经退行性变可能会影响大脑中甲状腺激素（TH）的代谢，导致局部脑 HPT。因此，本综述旨在阐明 HPT 与 AD 之间的潜在关联。HPT 通过诱导淀粉样β（Aβ）和 tau 蛋白磷酸化的产生，以及突触可塑性和记忆功能障碍的发展，促进 AD 的进展。此外，由于 Aβ和 tau 蛋白磷酸化的积累，TH 的代谢在 AD 中失调，导致局部脑 HPT。此外，HPT 可以通过多种机制途径影响 AD 神经病理学，包括转甲状腺素蛋白失调、氧化应激、内质网应激、自噬功能障碍、线粒体功能障碍和脑源性神经营养因子抑制。总之，HPT 和 AD 之间存在潜在联系，因为 HPT 对 AD 神经病理学有不利影响，反之亦然。
