Impact of social isolation on microglia activation in cerebral amyloid angiopathy
Description: Preserving cognitive health in old age ranks among the most important public health challenges. With aging, the prevalence of cerebral amyloid angiopathy (CAA), a cerebral small vessel disease characterized by amyloid deposition in the cortical and leptomeningeal vasculature, significantly increases. CAA is a largely untreatable cause of intracerebral hemorrhage and dementia. Studies estimate an 85-95% prevalence of CAA among Alzheimer’s disease patients and 10-50% among the general elderly population, positioning CAA as one of the strongest vascular contributors to age-related cognitive impairment. With aging, the prevalence of social isolation also increases, especially in women. Census data shows that over 50% of women over age 80 now live alone. Individuals with limited social contacts and self-reported loneliness have an increased risk of dementia and heightened inflammatory and metabolic responses to stress. However, it is not known if isolation increases amyloid deposition on the cerebral vasculature, or if isolation exacerbates CAA-induced cognitive decline. Microglia, as brain-resident immune cells, play critical roles in the surveillance of and response to pathological insults to the brain. While it has been established that microglia are activated in the presence of blood-brain barrier leakage, evidence for the contribution of microglia to the initiation of cerebrovascular dysfunction and subsequent cognitive decline in CAA remains limited. Sex differences are present in many of the neurodegenerative diseases that affect brain health, including CAA. Recent single-cell sequencing studies have also shown fundamental sex differences in microglia. Whether sex differences in microglial function influence CAA progression is unknown. In this proposal, by using a combination of molecular and cellular techniques, we will test the hypothesis that social isolation polarizes microglia towards a proinflammatory phenotype, reducing their ability to maintain brain vascular integrity, thereby worsening CAA outcomes in a sex-specific manner. Addressing these questions will help identify mechanisms by which social isolation impacts microglial function and brain inflammation, which is likely important to many age-related diseases that pose a threat to brain health. This proposal will contribute to the long-term goal of understanding the mechanisms underlying aging-related cognitive decline in otherwise healthy older adults as well as those who suffer from aging.
Funder: American Heart Association
Amount: $156,600
Funding type: fellowship
Funder scheme: Postdoctoral Fellowship
Start date: 2025-01-01
End date: 2026-12-31
Investigators: Danye Jiang, Danye Jiang
Institution: The University of Texas Health Science Center at Houston
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 25POST1374453
OpenAlex ID: G6563225739