The Rockefeller University

Developing Directly Reprogrammed Human Neurons to Investigate the Molecular Basis of Neurodegeneration in HIV and Aging

Purpose

The prevalence of HIV-1 associated neurocognitive disorders (HANDs) is 30%-50%. Advancing age is strongly associated with increased HAND prevalence and investigating the molecular basis of synaptodendritic injury and neurocognitive decline in this context is paramount. Recently the ability to generate directly induced neurons (iNs) from patient-derived fibroblasts has been demonstrated. Unlike the immature neuronal populations generated from induced pluripotent stem cells (iPSCs) iNs reportedly retain aging-associated characteristics of the donor. In this proposal we aim to develop directly induced neurons (iNs) from HIVnegative individuals that retain age-associated transcriptional signatures. We will then determine if directly induced neurons (iNs) derived from HIV-positive individuals reveal age- and additional HIV disease-associated transcriptional signatures.