Hyman Lab Hyman Lab

APOE and Neurodegenerative Diseases

APOE and Neurodegenerative Diseases

Project Overview

Apolipoprotein E (APOE) is a lipid transport protein primarily expressed by astrocytes and microglia in the central nervous system; it plays a multifaceted role in maintaining blood-brain barrier (BBB) integrity and regulating neuroinflammation. Since neuroinflammation and abnormal cytoplasmic accumulations are pathological hallmarks in almost all patients with Alzheimer’s disease, we investigate the mechanistic underpinnings by which APOE4 disrupts astrocyte-endothelial signaling and leads to BBB permeability. Recent work highlights how the APOEε4 allele might prime microglia towards a phagocytic state and how these changes result from a cell-specific gain of function effect of ApoE4. We are also investigating the potential attenuation of Alzheimer’s symptoms through APOE ε2 via gene therapy approaches.

Publications

  • Jackson, R. et al. (2022). “APOE4 derived from astrocytes leads to blood-brain barrier impairment.” Brain 145(10),3582-3593.
  • Jackson, R. et al. (2024). “Multifaceted roles of APOE in Alzheimer disease.” Nature Reviews neurology 20(8):457-474.
  • Jackson, R. et al. (2024). “APOE2 gene therapy reduces amyloid deposition and improves markers of neuroinflammation and neurodegeneration in a mouse model of Alzheimer disease.” Molecular Therapy
Research Areas
Aging Alzheimer's Disease Amyloid-Beta Amyloid-Beta Plaques APOE APOE2 APOE4 Astrocytes Blood-Brain Barrier Brain Heterogeneity Burst Firing Cell Death Pathways Cryptic Splicing Endothelial Cells Gene Therapy Glial Transcriptome Hippocampal Neurons Mouse Models Myeloid Cells Neurodegeneration Neurofibrillary Tangles Neuronal Genomics Post-Translational Modifications Protein Abundance Somatic Mutations Tau Tau Pathology Tauopathy TDP-43 Transcriptomics Ubiquitin-Proteasome System
Tags
Gene Regulation Grant NIH