Peripheral lipid oxidative stress markers are related to vascular risk factors and subcortical small vessel disease

Neurobiol Aging. 2017 Nov;59:91-97. doi: 10.1016/j.neurobiolaging.2017.06.029. Epub 2017 Jul 11.


Subcortical white matter hyperintensities (WMH), presumed to indicate small vessel ischemic vascular disease, are found commonly in elderly individuals with and without Alzheimer's disease (AD). Oxidative stress may instigate or accelerate the development of vascular disease, and oxidative stress markers are elevated in AD. Here, we assess independent relationships between three serum lipid peroxidation markers (lipid hydroperoxides [LPH], 8-isoprostane, and 4-hydroxynonenal) and the presence of extensive subcortical WMH and/or AD. Patients were recruited from memory and stroke prevention clinics into four groups: minimal WMH, extensive WMH, AD with minimal WMH, and AD with extensive WMH. Extensive WMH, but not AD, was associated with higher serum concentrations of 8-isoprostane and LPH. Peripheral LPH concentrations mediated the effect of hypertension on deep, but not periventricular, WMH volumes. 4-hydroxynonenal was associated with hyperlipidemia and cerebral microbleeds, but not with extensive WMH or AD. We conclude that lipid peroxidation mediates hypertensive injury to the deep subcortical white matter and that peripheral blood lipid peroxidation markers indicate subcortical small vessel disease regardless of an AD diagnosis.

Keywords: Cerebrovascular disease; Oxidative stress; Small vessel disease; White matter hyperintensities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aldehydes / blood
  • Alzheimer Disease / complications
  • Biomarkers / blood
  • Cerebral Small Vessel Diseases / diagnosis*
  • Cerebral Small Vessel Diseases / diagnostic imaging
  • Cerebral Small Vessel Diseases / etiology*
  • Cohort Studies
  • Cross-Sectional Studies
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Female
  • Humans
  • Hypertension / complications
  • Lipid Peroxidation
  • Lipid Peroxides / blood
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Oxidative Stress*
  • Risk Factors
  • White Matter / diagnostic imaging


  • Aldehydes
  • Biomarkers
  • Lipid Peroxides
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • 4-hydroxy-2-nonenal