ALZHEIMERS RESEARCH PROJECT: Studying Primate-Specific Neuronal Vulnerability in Neurodegeneration Using Human and Non-Human Primate Brain Organotypic Slice Cultures

National Institute On Aging

Investigators

Abstract

This study uses human and non-human primate organotypic brain slice cultures to explore cellular and molecular changes that may underlie neurodegenerative disease pathogenesis. Brain slices are cultured from human epilepsy surgery resected tissue and post-mortem non-human primates, providing a unique opportunity to study primate-specific neuronal subtypes and neurodegeneration mechanisms across multiple brain regions. To induce neurodegeneration in control organotypic slices, a range of tools is employed, including small molecules, iPS-derived glial cells, and CRISPR/Cas9 gene editing to introduce disease-associated mutations. The study will assess both cell-autonomous and non-cell-autonomous contributions to neurodegeneration, with a focus on why some neurons are more resilient or vulnerable and how glia cells contribute to this process. A variety of experimental readouts—including single-cell and spatial transcriptomics, proteomics, electrophysiology, and immunohistology—will be used to evaluate tissue response, glial impact, and mutations effects on neuronal integrity and function. This project is conducted in collaboration with Dr. Kareem Zaghloul (NINDS), who provides access to epilepsy tissue, and Dr. Hugo Tejeda (NIMH), who supports electrophysiological recordings and analysis. We are also part of the NIH Non-Human Primate Consortium. Together, these efforts will create a physiologically relevant platform for dissecting the mechanisms driving neurodegeneration and neuronal vulnerability.