Molecular Signatures of Resilience to Alzheimer's Disease in Neocortical Layer 4 Neurons.

ABSTRACT: Single-cell omics is advancing our understanding of selective neuronal vulnerability in Alzheimer's disease (AD), revealing specific subtypes that are either susceptible or resilient to neurodegeneration. Using single-nucleus and spatial transcriptomics to compare neocortical regions affected early (prefrontal cortex and precuneus) or late (primary visual cortex) in AD, we identified a resilient excitatory population in layer 4 of the primary visual cortex expressing RORB, CUX2, and EYA4. Layer 4 neurons in association neocortex also remained relatively preserved as AD progressed and shared overlapping molecular signatures of resilience. Early in the disease, resilient neurons upregulated genes associated with synapse maintenance, synaptic plasticity, calcium homeostas

SUBMITTER: Dharshini SAP 

PROVIDER: S-EPMC11580857 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature