Yanai Hidekatsu, Adachi Hiroki, Hakoshima Mariko, Katsuyama Hisayuki
Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa 272-8516, Chiba, Japan.
Molecules. 2024 Dec 16;29(24):5936. doi: 10.3390/molecules29245936.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cognitive dysfunction, memory decline, and behavioral disturbance, and it is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. Although various hypotheses have been proposed to explain the pathogenesis of AD, including the amyloid beta hypothesis, oxidative stress hypothesis, and abnormal phosphorylation of tau proteins, the exact pathogenic mechanisms underlying AD remain largely undefined. Furthermore, effective curative treatments are very limited. Epidemiologic studies provide convincing evidence for a significant association between type 2 diabetes and AD. Here, we showed energy metabolism using glucose, lactate, ketone bodies, and lipids as energy substrates in a normal brain, and changes in such energy metabolism due to type 2 diabetes. We also showed the influences of such altered energy metabolism due to type 2 diabetes on the pathology of AD. Furthermore, we comprehensively searched for risk factors related with type 2 diabetes for AD and showed possible therapeutic interventions based on considering risk factors and altered brain energy metabolism due to type 2 diabetes for the development of AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，伴有认知功能障碍、记忆力减退和行为紊乱，其病理特征是大脑中淀粉样斑块和神经原纤维缠结的积累。尽管已经提出了各种假说来解释AD的发病机制，包括β-淀粉样蛋白假说、氧化应激假说和tau蛋白异常磷酸化，但AD的确切致病机制在很大程度上仍不明确。此外，有效的治疗方法非常有限。流行病学研究为2型糖尿病与AD之间的显著关联提供了令人信服的证据。在这里，我们展示了正常大脑中以葡萄糖、乳酸、酮体和脂质作为能量底物的能量代谢，以及2型糖尿病导致的这种能量代谢变化。我们还展示了2型糖尿病导致的这种能量代谢改变对AD病理的影响。此外，我们全面搜索了与2型糖尿病相关的AD危险因素，并基于考虑危险因素和2型糖尿病导致的大脑能量代谢改变，展示了针对AD发展的可能治疗干预措施。
