Abstract：
The hypothalamus is the region of the brain that integrates the neuroendocrine system and whole-body metabolism. Patients with Alzheimer\'s disease (AD) have been reported to exhibit pathological changes in the hypothalamus, such as neurofibrillary tangles (NFTs) and amyloid plaques (APs). However, few studies have investigated whether hypothalamic AD pathology is associated with clinical factors. We investigated the association between AD-related pathological changes in the hypothalamus and clinical pictures using autopsied brain samples obtained from deceased residents of a Japanese community. A total of 85 autopsied brain samples were semi-quantitatively analyzed for AD pathology, including NFTs and APs. Our histopathological studies showed that several hypothalamic nuclei, such as the tuberomammillary nucleus (TBM) and lateral hypothalamic area (LHA), are vulnerable to AD pathologies. NFTs are observed in various neuropathological states, including normal cognitive cases, whereas APs are predominantly observed in AD. Regarding the association between hypothalamic AD pathologies and clinical factors, the degree of APs in the TBM and LHA was associated with a lower body mass index while alive, after adjusting for sex and age at death. However, we found no significant association between hypothalamic AD pathology and the prevalence of hypertension, diabetes, or dyslipidemia. Our study showed that a lower BMI, which is a poor prognostic factor of AD, might be associated with hypothalamic AP pathology and highlighted new insights regarding the disruption of the brain-whole body axis in AD.
摘要：
下丘脑是整合神经内分泌系统和全身代谢的大脑区域。据报道，患有阿尔茨海默病（AD）的患者表现出下丘脑的病理变化，如神经原纤维缠结（NFT）和淀粉样蛋白斑（AP）。然而,很少有研究调查下丘脑AD病理是否与临床因素相关。我们使用从日本社区已故居民那里获得的尸检脑样本，调查了下丘脑中与AD相关的病理变化与临床图片之间的关联。共对85份尸检的脑样本进行AD病理半定量分析，包括NFT和AP。我们的组织病理学研究表明，下丘脑的几个核，如结节乳核（TBM）和下丘脑外侧区（LHA），容易受到AD病理的影响。在各种神经病理学状态下观察到NFT，包括正常的认知情况，而AP主要在AD中观察到。关于下丘脑AD病理与临床因素之间的关系，TBM和LHA中AP的程度与活着时的较低体重指数相关，在调整了死亡时的性别和年龄后。然而,我们发现下丘脑AD病理与高血压患病率之间没有显著关联，糖尿病,或血脂异常。我们的研究表明，较低的BMI，这是AD的不良预后因素，可能与下丘脑AP病理有关，并强调了有关AD中脑-全身轴破坏的新见解。
