Pathology and Treatments of Alzheimer's Disease Based on Considering Changes in Brain Energy Metabolism Due to Type 2 Diabetes

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2025 Jan 8

PMID 39770025

Authors

Hidekatsu Yanai

Hiroki Adachi

Mariko Hakoshima

Hisayuki Katsuyama

Affiliations

Soon will be listed here.

Abstract

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.

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