Luci Roberts
$234,000
UNIVERSITY OF MICHIGAN AT ANN ARBOR
Michigan
National Institute on Aging (NIA)
More than 85 million cases of COVID-19 have been recorded in the US alone, and up to 40% of survivors report Long-COVID symptoms including cognitive impairments. Together with evidence that inflammation during adulthood increases risk for later cognitive decline, this raises the prospect that the COVID-19 pandemic will cause a future “second pandemic” in Alzheimer’s disease and age-related dementias. In this project, we will identify specific mechanisms by which single stranded RNA (ssRNA) viruses (e.g., SARS-COV- 2) triggered innate immune signaling contributes to long-lasting memory impairments, exaggerated cognitive decline during aging, and risk for dementias including Alzheimer’s disease. Our main goal is to determine the impact of innate immune signaling as a consequence of ssRNA viruses on exaggeration of age-related cognitive decline and risk for dementias including Alzheimer’s Disease. We will use a subchronic inflammation protocol, established in my laboratory, together with behavioral tests of memory, protein biochemistry, and gene expression assays to identify persistent changes in inflammatory state and neuroplasticity mechanisms that exacerbate cognitive decline. We will use wild-type mice and APP/PS1 transgenic mice to determine whether TLR7-induced inflammation causes acceleration of age-related cognitive decline and AD-like pathology. Findings from this project will demonstrate how COVID-19, and other TLR7-induced inflammation increases risk for dementia; identify sex differences in COVID-related vulnerability to cognitive decline; and provide a basis for novel preventive strategies and treatments to reduce risk for Alzheimer’s disease and other dementias in the post-COVID-19 population.