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. A TSPO variant, rs6971, determines binding affinity of exogenous radioligands in 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.