Role of white matter hyperintensity in effects of apolipoprotein E on cognitive injury
Jacob Raber1, Lisa C Silbert2,3
1Departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, Division of Neuroscience, ONPRC, Oregon Health & Science University, Portland, OR, United States.
Abstract:
Magnetic Resonance Imaging (MRI) T2-weighted white matter hyperintensity (WMH) is a marker of small vessel cerebrovascular pathology and is of ischemic origin. The prevalence and severity of WMH is associated with cardiovascular risk factors, aging, and cognitive injury in mild cognitive impairment (MCI), vascular dementia, and Alzheimer's disease (AD). WMH especially affects executive function, with additional effects on memory and global cognition. Apolipoprotein E (apoE) plays a role in cholesterol metabolism and neuronal repair after injury. Human and animal studies support a role for apoE in maintaining white matter integrity. In humans, there are three major human apoE isoforms, E2, E3, and E4. Human apoE isoforms differ in risk to develop AD and in association with WMH. In this Mini Review, we propose an increased focus on the role of WMH in cognitive health and cognitive injury and the likely role of apoE and apoE isoform in modulating these effects. We hypothesize that apoE and apoE isoforms play a role in modulating WMH via apoE isoform-dependent effects on oxylipins and 7-ketocholesterol, as well as amyloid related vascular injury, as seen in cerebral amyloid angiopathy.
Insights
White matter hyperintensities (WMH) on MRI indicate cerebrovascular damage impacting cognition. This review explores how Apolipoprotein E (apoE) isoforms may influence WMH and cognitive health.
Area of Science:
- Neuroimaging
- Neurology
- Genetics
Background:
- White matter hyperintensities (WMH) on T2-weighted MRI signify small vessel ischemic cerebrovascular disease.
- WMH prevalence and severity correlate with aging, cardiovascular risks, and cognitive decline in conditions like mild cognitive impairment, vascular dementia, and Alzheimer's disease.
- WMH particularly impairs executive function, memory, and global cognition.
Purpose of the Study:
- To highlight the significance of WMH in cognitive health and injury.
- To investigate the role of Apolipoprotein E (apoE) and its isoforms in modulating WMH.
- To propose mechanisms by which apoE isoforms influence WMH, including effects on oxylipins, 7-ketocholesterol, and amyloid-related vascular injury.
Main Methods:
- Review of existing human and animal studies on WMH and apoE.
- Analysis of the association between apoE isoforms (E2, E3, E4) and WMH.
- Exploration of potential molecular pathways linking apoE to white matter integrity.
Main Results:
- Apolipoprotein E (apoE) is crucial for maintaining white matter integrity.
- Human apoE isoforms (E2, E3, E4) exhibit differential associations with Alzheimer's disease risk and WMH.
- Evidence suggests apoE influences WMH through lipid metabolism and vascular injury pathways.
Conclusions:
- WMH are a critical factor in cognitive impairment and injury.
- Apolipoprotein E (apoE) and its isoforms likely play a significant role in modulating WMH.
- Further research into apoE's role in WMH could reveal new therapeutic targets for cognitive disorders.
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