Increasing hexokinase 1 expression improves mitochondrial and glycolytic functional deficits seen in sporadic Alzheimer's disease astrocytes.

ABSTRACT: Abnormalities in cellular metabolism are seen early in Alzheimer's disease (AD). Astrocyte support for neuronal function has a high metabolic demand, and astrocyte glucose metabolism plays a key role in encoding memory. This indicates that astrocyte metabolic dysfunction might be an early event in the development of AD. In this paper we interrogate glycolytic and mitochondrial functional changes and mitochondrial structural alterations in patients' astrocytes derived with a highly efficient direct conversion protocol. In astrocytes derived from patients with sporadic (sAD) and familial AD (fAD) we identified reductions in extracellular lactate, total cellular ATP and an increase in mitochondrial reactive oxygen species. sAD and fAD astrocytes displayed significant reductions in mitochondri

SUBMITTER: Bell SM 

PROVIDER: S-EPMC11919762 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature