Investigating the Impact of Novel Senescent Microglia in Alzheimer's Disease Progression

Title: Inves�ga�ng the Impact of Novel Senescent Microglia in Alzheimer's Disease Pathology Abstract: Alzheimer's Disease (AD) is a debilita�ng neurodegenera�ve disorder with a cri�cal need for improved therapeu�c strategies. One controversial component of AD progression is the role of microglia, the brain's immune cells. Recent research indicates a subpopula�on of these cells exhibi�ng senescence characteris�cs, raising the ques�on if these senescent microglia might contribute to AD progression through a senescence-associated secretory phenotype (SASP). Our proposal aims to elucidate the role of these cells in AD using a two-fold approach: defining and characterizing these senescent microglia through proteomic, transcriptomic, and spa�al-omics profiling (Aim 1) and inves�ga�ng whether removing these senescent microglia can slow or delay AD progression (Aim 2). We plan to leverage a novel transgenic mouse model to selec�vely ablate newly iden�fied senescent microglia and assess the subsequent impact on AD progression. If successful, these studies could offer novel insight into AD pathology and iden�fy poten�al therapeu�c targets by focusing on the selec�ve elimina�on of senescent microglia.