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

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

Author information

1
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Canada; Cardiovascular Prevention and Rehabilitation Program, University Health Network Toronto Rehabilitation Institute, Toronto, Canada. Electronic address: w.swardfager@utoronto.ca.
2
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Canada.
3
Anxiety and Mood Disorders Department, Centre for Addictions and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
4
Departamento Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.
5
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.
6
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.
7
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
8
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada; Cardiovascular Prevention and Rehabilitation Program, University Health Network Toronto Rehabilitation Institute, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
9
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.
10
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada; Department of Medicine (Neurology Division), University of Toronto, Toronto, Canada.
11
Department of Medicine (Neurology Division), McMaster University, Hamilton, Canada.
12
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Clinical Pathology, Sunnybrook Health Sciences Centre, Toronto, Canada.
13
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Canada.
14
Department of Medicine (Neurology Division) and the Northern Medical Program, University of British Columbia, Prince George, Canada.
15
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada; Anxiety and Mood Disorders Department, Centre for Addictions and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
16
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada; Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Canada; LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Canada; Department of Medicine (Neurology Division), University of Toronto, Toronto, Canada.

Abstract

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

[Indexed for MEDLINE]

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