Multi-region brain transcriptomic analysis of amyotrophic lateral sclerosis reveals widespread RNA alterations and substantial cerebellum involvement.

ABSTRACT:

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects the motor neurons, causing progressive muscle weakness and paralysis. While research has focused on understanding pathological mechanisms in the motor cortex and spinal cord, there is growing evidence that extra-motor brain regions may also play a role in the pathogenesis or progression of ALS.

Methods

We generated 165 sample-matched post-mortem brain transcriptomes from 22 sporadic ALS patients with pTDP-43 pathological staging and 11 non-neurological controls. For each individual, five brain regions underwent mRNA sequencing: motor cortex (pTDP-43 inclusions always present), prefrontal cortex and hippocampus (pTDP-43 inclusions sometimes present), and occipital cortex and c

SUBMITTER: Grima N 

PROVIDER: S-EPMC12023386 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature