Introduction: Synaptic damage is a key pathology of Alzheimer's disease (AD). The mechanism underlying synaptic vulnerability in AD remains elusive. Methods: Using a large-scale transcriptomic dataset, we analyzed the neurogranin-centered integrative gene network and assessed the correlation of neurogranin (NRGN) gene expression with AD pathology in post mortem brains. We studied the association of NRGN expression with Clinical Dementia Rating (CDR) and neuropathological diagnosis of AD. Results: We find that the genes positively correlated with NRGN expression in AD are involved in synaptic transmission and cation channel pathways. NRGN expression is correlated with amyloid and tau pathology in the perirhinal cortex of post mortem brains. NRGN expression is associated with the diagnosis of AD and correlated with CDR. Discussion: Transcriptional regulation of the gene encoding for synaptic protein is involved in selective synaptic damage in AD. Identifying the genes associated with synaptic damage pathways in AD may provide targets for intervention.
|Alzheimer's and Dementia: Translational Research and Clinical Interventions
|Published - 2021
- Alzheimer's disease
- integrative gene network
- perirhinal cortex