Cerebrovascular and microglial states are not altered by functional neuroinflammatory gene variant

Daniel Felsky; Philip L De Jager; Julie A Schneider; Konstantinos Arfanakis; Debra A Fleischman; Zoe Arvanitakis; William G Honer; Jennie G Pouget; Romina Mizrahi; Bruce G Pollock; James L Kennedy; David A Bennett; Aristotle N Voineskos; authors of the Alzheimer’s Disease Neuroimaging Initiative

doi:10.1177/0271678X15626719

Cerebrovascular and microglial states are not altered by functional neuroinflammatory gene variant

J Cereb Blood Flow Metab. 2016 Apr;36(4):819-30. doi: 10.1177/0271678X15626719. Epub 2016 Jan 13.

Authors

Affiliations

¹ Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada Institute of Medical Science, University of Toronto, King's College Circle, Toronto, ON, Canada.
² Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
³ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁴ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA Department of Biomedical Engineering, Illinois Institute of Technology, IL, USA.
⁵ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA.
⁶ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
⁷ BC Mental Health and Addictions Research Institute, University of British Columbia, Vancouver, BC, Canada.
⁸ Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada Institute of Medical Science, University of Toronto, King's College Circle, Toronto, ON, Canada aristotle.voineskos@camh.ca.

Abstract

The translocator protein, a microglial-expressed marker of neuroinflammation, has been implicated in Alzheimer's disease, which is characterized by alterations in vascular and inflammatory states. ATSPOvariant, rs6971, determines binding affinity of exogenous radioligandsin vivo; however, the effect of these altered binding characteristics on inflammatory and cerebrovascular biomarkers has not been assessed. In 2345 living subjects (Alzheimer's Disease Neuroimaging Initiative, n = 1330) and postmortem brain samples (Religious Orders Study and Memory and Aging Project, n = 1015), we analyzed effects of rs6971 on white matter hyperintensisites, cerebral infarcts, circulating inflammatory biomarkers, amyloid angiopathy, and microglial activation. We found that rs6971 does not alter translocator protein in a way that impacts cerebrovascular and inflammatory states known to be affected in dementia.

Keywords: Alzheimer’s; MRI; Microglia; genetics; inflammation; risk factors; white matter disease.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aging / pathology
Alzheimer Disease / pathology
Arterial Pressure
Biomarkers / analysis
Brain / pathology
Cerebral Amyloid Angiopathy / genetics
Cerebral Amyloid Angiopathy / pathology
Cerebral Infarction / pathology
Cerebrovascular Circulation / genetics*
Female
Genetic Variation
Humans
Inflammation / genetics*
Male
Microglia*
Reactive Oxygen Species / metabolism
White Matter / pathology

Cerebrovascular and microglial states are not altered by functional neuroinflammatory gene variant

Authors

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Abstract

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