Plasma High Density Lipoprotein Small Subclass is Reduced in Alzheimer's Disease Patients and Correlates with Cognitive Performance

J Alzheimers Dis. 2020;77(2):733-744. doi: 10.3233/JAD-200291.


Background: The link between cholesterol and Alzheimer's disease (AD) has received much attention, as evidence suggests high levels of cholesterol might be an AD risk factor. The carriage of cholesterol and lipids through the body is mediated via lipoproteins, some of which, particularly apolipoprotein E (ApoE), are intimately linked with AD. In humans, high density lipoprotein (HDL) is regarded as a "good" lipid complex due to its ability to enable clearance of excess cholesterol via 'cholesterol reverse transport', although its activities in the pathogenesis of AD are poorly understood. There are several subclasses of HDL; these range from the newly formed small HDL, to much larger HDL.

Objective: We examined the major subclasses of HDL in healthy controls, mild cognitively impaired, and AD patients who were not taking statins to determine whether there were HDL profile differences between the groups, and whether HDL subclass levels correlated with plasma amyloid-β (Aβ) levels or brain Aβ deposition.

Methods: Samples from AIBL cohort were used in this study. HDL subclass levels were assessed by Lipoprint while Aβ1-42 levels were assessed by ELISA. Brain Aβ deposition was assessed by PET scan. Statistical analysis was performed using parametric and non-parametric tests.

Results: We found that small HDL subclass is reduced in AD patients and it correlates with cognitive performance while plasma Aβ concentrations do not correlate with lipid profile or HDL subfraction levels.

Conclusion: Our data indicate that AD patients exhibit altered plasma HDL profile and that HDL subclasses correlate with cognitive performances.

Keywords: Amyloid-β; apolipoprotein; blood; cholesterol; lipid transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / psychology*
  • Amyloid beta-Peptides / blood*
  • Amyloid beta-Peptides / genetics
  • Biomarkers / blood
  • Cognition / physiology*
  • Cohort Studies
  • Female
  • Humans
  • Lipoproteins, HDL / blood*
  • Lipoproteins, HDL / genetics
  • Male
  • Peptide Fragments / blood*
  • Peptide Fragments / genetics
  • Psychomotor Performance / physiology*


  • Amyloid beta-Peptides
  • Biomarkers
  • Lipoproteins, HDL
  • Peptide Fragments
  • amyloid beta-protein (1-42)