AUTHOR=Fan Li-Yuan , Yang Jing , Li Ming-Li , Liu Ruo-Yu , Kong Ying , Duan Su-Ying , Guo Guang-Yu , Yang Jing-Hua , Xu Yu-Ming 

TITLE=Single-nucleus transcriptional profiling uncovers the reprogrammed metabolism of astrocytes in Alzheimer’s disease

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=16

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2023.1136398

DOI=10.3389/fnmol.2023.1136398

ISSN=1662-5099

ABSTRACT=<p>Astrocytes play an important role in the pathogenesis of Alzheimer’s disease (AD). It is widely involved in energy metabolism in the brain by providing nutritional and metabolic support to neurons; however, the alteration in the metabolism of astrocytes in AD remains unknown. Through integrative analysis of single-nucleus sequencing datasets, we revealed metabolic changes in various cell types in the prefrontal cortex of patients with AD. We found the depletion of some important metabolites (acetyl-coenzyme A, aspartate, pyruvate, 2-oxoglutarate, glutamine, and others), as well as the inhibition of some metabolic fluxes (glycolysis and tricarbocylic acid cycle, glutamate metabolism) in astrocytes of AD. The abnormality of glutamate metabolism in astrocytes is unique and important. Downregulation of <italic>GLUL</italic> (<italic>GS</italic>) and <italic>GLUD1</italic> (<italic>GDH</italic>) may be the cause of glutamate alterations in astrocytes in AD. These results provide a basis for understanding the characteristic changes in astrocytes in AD and provide ideas for the study of AD pathogenesis.</p>