Description

The Genetic and Population Architecture of Aged Human Microglia: Role in Accelerating Tau Pathology and Cognitive Decline

Philip L. De Jager

Columbia University Medical Center

The renewed interest in the role of peripheral and central myeloid cells in neurodegenerative diseases has been spurred by human genetic studies, particularly those in Alzheimer’s disease. However, we still understand little of the extent of intra- and inter-individual variability in myeloid subpopulations present in the older brain. Further, we know little of the regulatory apparatus that governs their plasticity and myriad of functional roles. In this talk, we will review new data outlining 16 different subsets of microglia and other myeloid cells present within the aging human brain. We will discuss the properties of each subset, and the extent to which certain subsets of these cells are implicated in the neuropathologies of aging. Preliminary results suggest that the more “microglial” subpopulations are less enriched for genes associated with Alzheimer-related pathologies than the myeloid subsets that bear microglial as well as other markers. Further, complementary analytic approaches using human immunohistochemical data and RNA sequencing data suggest that these myeloid cells appear to have an important role in the accumulation of Tau pathology which then leads to cognitive decline. Thus, we present an atlas of human microglial/myeloid subpopulations found in the aging human brain and dissect the role of some of these cells in the deposition of Tau pathology when they are activated.