This page provides a comprehensive reference for gene expression patterns in the brain across neurodegenerative diseases, leveraging data from the Allen Brain Atlas and other comprehensive expression studies. Understanding where genes are expressed in the brain is fundamental to interpreting GWAS findings, identifying cell-type-specific vulnerability, and developing targeted therapies. [1]
Gene expression patterns reveal which cell types express disease-relevant genes, providing insights into mechanism and potential therapeutic windows. Single-cell RNA sequencing has revolutionized our understanding of cell-type-specific expression in neurodegenerative diseases. [2]
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Hippocampal Expression: The hippocampus shows early involvement in AD. Key genes with hippocampal expression include: [4]
Entorhinal Cortex Expression: The entorhinal cortex is the earliest affected region: [5]
Cortical Expression: Neocortex shows later involvement:
Substantia Nigra Expression: The substantia nigra pars compacta is selectively vulnerable:
Striatal Expression: Target of dopaminergic therapy:
Neuronal Expression
Glial Expression
The Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) provides single-nucleus RNA sequencing of AD brains:
Cell-Type Vulnerability in AD
Cell-Type Vulnerability in PD
| Gene | eQTL Tissue | Effect | GWAS Overlap |
|---|---|---|---|
| AP0E | Brain | Lipid metabolism | Strong |
| CLU | Brain | Chaperone activity | Moderate |
| CR1 | Blood | Immune function | Strong |
| TREM2 | Brain | Microglial function | Strong |
| Gene | eQTL Tissue | Effect | GWAS Overlap |
|---|---|---|---|
| SNCA | Brain | Synaptic function | Strong |
| LRRK2 | Brain | Kinase activity | Strong |
| GBA1 | Blood | Lysosomal function | Moderate |
Genes with high brain expression that are also GWAS hits represent priority targets:
Neuronal targets: Synaptic proteins, ion channels, neurotransmitter receptors
Microglial targets: TREM2, CD33, complement components
Astrocytic targets: APOE, glutamate transporters
Oligodendroglial targets: Myelin genes, cholesterol metabolism
Brain Cell Type Atlas (2021). 2021. ↩︎
GTEx Consortium (2020). 2020. ↩︎
AD eQTL Meta-Analysis (2022). 2022. ↩︎