Novel insights into brain lipid metabolism in Alzheimer's disease: Oligodendrocytes and white matter abnormalities

FEBS Open Bio. 2024 Feb;14(2):194-216. doi: 10.1002/2211-5463.13661. Epub 2023 Jun 26.

Abstract

Alzheimer's disease (AD) is the most common cause of dementia. A genome-wide association study has shown that several AD risk genes are involved in lipid metabolism. Additionally, epidemiological studies have indicated that the levels of several lipid species are altered in the AD brain. Therefore, lipid metabolism is likely changed in the AD brain, and these alterations might be associated with an exacerbation of AD pathology. Oligodendrocytes are glial cells that produce the myelin sheath, which is a lipid-rich insulator. Dysfunctions of the myelin sheath have been linked to white matter abnormalities observed in the AD brain. Here, we review the lipid composition and metabolism in the brain and myelin and the association between lipidic alterations and AD pathology. We also present the abnormalities in oligodendrocyte lineage cells and white matter observed in AD. Additionally, we discuss metabolic disorders, including obesity, as AD risk factors and the effects of obesity and dietary intake of lipids on the brain.

Keywords: Alzheimer's disease; lipid metabolism in brain; myelin; oligodendrocytes; white matter.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / metabolism
  • Brain / metabolism
  • Genome-Wide Association Study
  • Humans
  • Lipid Metabolism
  • Lipids
  • Obesity / metabolism
  • Oligodendroglia
  • White Matter* / metabolism
  • White Matter* / pathology

Substances

  • Lipids