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June 1, 2021npj Aging and Mechanisms of DiseaseOpen Access

Abnormal brain cholesterol homeostasis in Alzheimer’s disease—a targeted metabolomic and transcriptomic study

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Authors

VVVijay R. VarmaHLHatice Büşra Lüleci̇AOAnup Mammen Oommen

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Overview

Metabolomic and transcriptomic analysis reveals impaired brain cholesterol synthesis and catabolism in Alzheimer's disease, suggesting potential targets for therapeutic intervention.

Key Points

  • To investigate whether brain cholesterol biosynthesis and catabolism are disrupted in Alzheimer's disease and explore their relationship with disease pathology.
  • Assessed metabolite markers of cholesterol biosynthesis and catabolism in postmortem brain autopsy samples from the Baltimore Longitudinal Study of Aging (BLSA) and Religious Orders Study (ROS) using linear mixed-effects models.
  • Analyzed gene expression regulators of cholesterol pathways across public brain transcriptomic datasets with ANOVA, contrasting changes against Parkinson's disease datasets.
  • Performed regional genome-scale metabolic network modeling to characterize specific alterations in cholesterol biosynthesis and catabolic reactions.
  • Identified pervasive abnormalities in brain cholesterol biosynthesis and catabolism in Alzheimer's disease that were absent in Parkinson's disease postmortem brain tissue.
  • Observed reduced de novo cholesterol biosynthesis alongside impaired enzymatic cholesterol catabolism and clearance, accompanied by the accumulation of cytotoxic oxysterols.

Cite This Study

Varma et al. (2021) studied this question.

synapsesocial.com/papers/69df02115ce7a5c5ecedbcc2https://doi.org/10.1038/s41514-021-00064-9
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