Alzheimer's disease is one of the most frequent forms of dementia. It is a progressive neurodegenerative disease, characterized by presence of amyloid plaques and neurofibrillary tangles in the brain. Obesity is regarded as abnormal fat accumulation with deleterious impact on human health. There is full scientific evidence that obesity and the metabolic comorbidities (e.g., insulin resistance, hyperglycaemia, and type 2 diabetes) are related to Alzheimer's disease and likely in the causative pathway. Numerous studies have identified several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammation. In this review, we present how obesity and the associated lipotoxicity as well as chronic inflammation initiate a state of insulin resistance that in turn, may have a role in causing the characteristic cerebral alterations of AD. In particular, we focus on the molecular mechanisms linking the obesity-induced impairment in insulin signalling to the upregulation of Aβ aggregation, tau hyper-phosphorylation, inflammation, oxidative stress and mitochondrial dysfunction.

阿尔茨海默病是最常见的痴呆形式之一。它是一种进行性神经退行性疾病，其特征是大脑中存在淀粉样斑块和神经原纤维缠结。肥胖被认为是对人体健康有害的异常脂肪堆积。有充分的科学证据表明肥胖和代谢合并症（例如、胰岛素抵抗、高血糖和 2 型糖尿病）与阿尔茨海默病有关，并且可能在致病途径中。许多研究已经确定了几种重叠的神经退行性机制，包括氧化应激、线粒体功能障碍和炎症。在这篇综述中，我们介绍了肥胖和相关的脂毒性以及慢性炎症如何引发胰岛素抵抗状态，而这种状态又可能在导致 AD 的特征性脑改变中起作用。特别是，我们专注于将肥胖引起的胰岛素信号传导损伤与 Aβ 聚集、tau 过度磷酸化、炎症、氧化应激和线粒体功能障碍的上调联系起来的分子机制。