Patricia and John Rosenwald Laboratory of Neurobiology & Genetics, The Rockefeller University, 1230 York Avenue, New York, NY, USA.
Transl Psychiatry. 2022 Jul 22;12(1):293. doi: 10.1038/s41398-022-02067-w.
Alzheimer's disease (AD) is a fatal cognitive disorder with proteinaceous brain deposits, neuroinflammation, cerebrovascular dysfunction, and extensive neuronal loss over time. AD is a multifactorial disease, and lifestyle factors, including diet, are likely associated with the development of AD pathology. Since obesity and diabetes are recognized as risk factors for AD, it might be predicted that a high-fat diet (HFD) would worsen AD pathology. However, modeling HFD-induced obesity in AD animal models has yielded inconclusive results. Some studies report a deleterious effect of HFD on Aβ accumulation, neuroinflammation, and cognitive function, while others report that HFD worsens memory without affecting AD brain pathology. Moreover, several studies report no major effect of HFD on AD-related phenotypes in mice, while other studies show that HFD might, in fact, be protective. The lack of a clear association between dietary fat consumption and AD-related pathology and cognitive function in AD mouse models might be explained by experimental variations, including AD mouse model, sex and age of the animals, composition of the HFD, and timeline of HFD consumption. In this review, we summarize recent studies that aimed at elucidating the effect of HFD-induced obesity on AD-related pathology in mice and provide an overview of the factors that may have contributed to the results reported in these studies. Based on the heterogeneity of these animal model studies and given that the human population itself is quite disparate, it is likely that people will benefit most from individualized nutritional plans based on their medical history and clinical profiles.
阿尔茨海默病（AD）是一种致命的认知障碍，其特征是存在蛋白沉积的脑组织、神经炎症、脑血管功能障碍和随着时间的推移广泛的神经元丧失。AD 是一种多因素疾病，生活方式因素，包括饮食，可能与 AD 病理的发展有关。由于肥胖和糖尿病被认为是 AD 的风险因素，因此可以预测高脂肪饮食（HFD）会加重 AD 病理。然而，在 AD 动物模型中模拟 HFD 诱导的肥胖产生了不一致的结果。一些研究报告 HFD 对 Aβ 积累、神经炎症和认知功能有有害影响，而另一些研究报告 HFD 恶化记忆而不影响 AD 大脑病理。此外，几项研究报告 HFD 对小鼠的 AD 相关表型没有重大影响，而其他研究表明 HFD 实际上可能具有保护作用。在 AD 小鼠模型中，饮食脂肪消耗与 AD 相关病理和认知功能之间缺乏明确关联可能是由于实验变异性引起的，包括 AD 小鼠模型、动物的性别和年龄、HFD 的组成以及 HFD 消耗的时间线。在这篇综述中，我们总结了最近旨在阐明 HFD 诱导的肥胖对小鼠 AD 相关病理影响的研究，并概述了可能导致这些研究报告结果的因素。基于这些动物模型研究的异质性，并且考虑到人类群体本身非常多样化，根据他们的病史和临床特征制定个性化的营养计划可能会使人们受益最大。
