Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndrome.

ABSTRACT: We elucidated the molecular fingerprint of vulnerable excitatory neurons within select cortical lamina of individuals with Down syndrome (DS) for mechanistic understanding and therapeutic potential that also informs Alzheimer's disease (AD) pathophysiology. Frontal cortex (BA9) layer III (L3) and layer V (L5) pyramidal neurons were microisolated from postmortem human DS and age- and sex-matched controls (CTR) to interrogate differentially expressed genes (DEGs) and key biological pathways relevant to neurodegenerative programs. We identified > 2300 DEGs exhibiting convergent dysregulation of gene expression in both L3 and L5 pyramidal neurons in individuals with DS versus CTR subjects. DEGs included over 100 triplicated human chromosome 21 genes in L3 and L5 neurons, demonstrating a trisom

SUBMITTER: Alldred MJ 

PROVIDER: S-EPMC11578391 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature