The brain cells in Alzheimer’s disease patients differ extensively from healthy brain cells at the molecular level: there are hundreds of genes that are normally active in the brain, but become inactive in Alzheimer’s. Similarly, Alzheimer’s disease appears to turn on hundreds of genes that are normally inactive in the brain. We have recently found that degradation of RNA molecules, which are the gene products that carry the genetic information in the cell, plays an important role in mediating these changes in Alzheimer’s. However, the identity and nature of the cellular factors that lead to irregular degradation of RNAs remain mostly unknown. In this project, we will study genomic data from hundreds of individuals and laboratory models of Alzheimer’s to understand what factors drive the irregular RNA degradation in the brain cells, and how they contribute to the cellular changes that we observe in the brain of Alzheimer’s disease patients. We will also examine the role of these molecular factors in different cell types of the brain, in order to understand their functions in the brain and the cell types that are affected by their malfunction in Alzheimer’s. These studies provide new insights into the fundamental biology of brain, factors that contribute to Alzheimer’s, and potential strategies for development of new therapeutic approaches.