The role of late life depression in cognitive decline and Alzheimer’s Disease risk Abstract The risk of developing Alzheimer’s Disease increases by three-fold for people who experience symptoms of depression in older age. Therefore, depression is thought to be a modifiable risk factor or early indicator of Alzheimer’s Disease. Yet, the link between depression and Alzheimer’s Disease is poorly understood. The aim of this administrative supplement to parent R01 MH128286 is to elucidate the link between depression and Alzheimer’s Disease. In Aim 1, we will identify brain mechanisms that are shared between depression and cognitive decline in older age. In Aim 2, we will determine the pathway through which depression impacts the development of Alzheimer’s Disease pathophysiology by comparing models to assess whether depression is an independent risk factor, an accelerator, an early indicator, or a response to Alzheimer’s Disease. All aspects in this administrative supplemental proposal fit within the scope of the parent R01, as we will leverage the same cohort (UK Biobank) and data variables (neuroimaging, depression scores, cognitive tests, and genetic risk factors). If funded, this supplement will offer a bridge to the PI to establish a track record and set up collaborations for expanded research into Alzheimer’s Disease and related dementias. The follow-up R01 proposal leveraging the results from this seed funding is expected to focus on the relationship between neuropsychiatric symptoms and preclinical markers (i.e., tau and amyloid beta) of Alzheimer’s Disease.