title: Cerebrovascular and microglial states are not altered by functional neuroinflammatory gene variant.
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.
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Felsky
authors.affiliation: 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.
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA Department of Biomedical Engineering, Illinois Institute of Technology, IL, USA.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Arfanakis
authors.affiliation: 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.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Fleischman
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Arvanitakis
authors.affiliation: BC Mental Health and Addictions Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: William G
authors.initials: WG
authors.lastname: Honer
authors.affiliation: 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.
authors.forename: Jennie G
authors.initials: JG
authors.lastname: Pouget
authors.affiliation: 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.
authors.forename: Romina
authors.initials: R
authors.lastname: Mizrahi
authors.affiliation: 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.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.affiliation: 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.
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: 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.
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000473:pathology; D062186:Arterial Pressure; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D017628:Microglia; D017382:Reactive Oxygen Species / Q000378:metabolism; D066127:White Matter / Q000473:pathology
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species
keywords: Alzheimer’s; MRI; Microglia; genetics; inflammation; risk factors; white matter disease