Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer's Disease

Cell Stem Cell. 2015 Oct 1;17(4):397-411. doi: 10.1016/j.stem.2015.08.001. Epub 2015 Aug 27.


Lipid metabolism is fundamental for brain development and function, but its roles in normal and pathological neural stem cell (NSC) regulation remain largely unexplored. Here, we uncover a fatty acid-mediated mechanism suppressing endogenous NSC activity in Alzheimer's disease (AD). We found that postmortem AD brains and triple-transgenic Alzheimer's disease (3xTg-AD) mice accumulate neutral lipids within ependymal cells, the main support cell of the forebrain NSC niche. Mass spectrometry and microarray analyses identified these lipids as oleic acid-enriched triglycerides that originate from niche-derived rather than peripheral lipid metabolism defects. In wild-type mice, locally increasing oleic acid was sufficient to recapitulate the AD-associated ependymal triglyceride phenotype and inhibit NSC proliferation. Moreover, inhibiting the rate-limiting enzyme of oleic acid synthesis rescued proliferative defects in both adult neurogenic niches of 3xTg-AD mice. These studies support a pathogenic mechanism whereby AD-induced perturbation of niche fatty acid metabolism suppresses the homeostatic and regenerative functions of NSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / metabolism
  • Adult Stem Cells / pathology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Animals
  • Autopsy
  • Cell Proliferation
  • Disease Models, Animal
  • Lipid Metabolism*
  • Mass Spectrometry
  • Mice
  • Microarray Analysis
  • Neural Stem Cells* / metabolism
  • Neural Stem Cells* / pathology
  • Oleic Acid / biosynthesis
  • Prosencephalon / metabolism*
  • Regeneration
  • Stem Cell Niche


  • Oleic Acid

Associated data

  • GEO/GSE60460