Title: Disrupted Autocrine IGF1 Signaling in VIP+ Interneurons as a Mechanism for Circuit Dysfunction in Alzheimer’s Disease

Insulin-like growth factor 1 (IGF1) is a neurotrophic hormone implicated in Alzheimer’s disease (AD) and age-related cognitive decline. While largely produced in the periphery, IGF1 can cross the blood brain barrier in an activity dependent manner, affecting learning and memory by modulating neural plasticity and excitability. Brain uptake of serum IGF1 has been shown to be impaired in AD patients, leading to less bioavailable IGF1 in the brain. Despite this, the role of IGF1 in AD has remained contentious due to conflicting reports of deleterious and neuroprotective actions. I propose that this difference may arise due to cell-type specific homeostatic IGF1 signaling and that IGF1’s neuroprotection can be unlocked by targeting specific brain cell types. I will characterize the expression of this hormone in the AD brain and test whether restoring IGF1 signaling in neural circuits involved in memory recall can restore normal function.