Multi-omic study identifies synaptic changes linked to C9ORF72-related disease
Original source
Integrative synaptosome multi-omics reveals disrupted synapse organization and localized cryptic transcripts in C9ORF72 -Frontotemporal Dementia. (opens in a new tab)Compass summarised this from the study's abstract.
Study details
- Studied in
- Human
- Peer review
- Preprint, not yet peer reviewed
Population inferred from the title and abstract by Compass.
Related topics
Researchers found changes in proteins, gene activity and RNA splicing in synapses from people with C9ORF72-related frontotemporal dementia (FTD). Patient-derived neurons also showed reduced synaptic markers and progressively impaired network activity. The work identified abnormally spliced transcripts, including KALRN and STMN2, within synaptic compartments.
Why this matters
C9ORF72 repeat expansions are a genetic cause of both FTD and amyotrophic lateral sclerosis (ALS), so the findings point to synaptic processes that may be relevant to some ALS cases. However, this is molecular and cellular research and does not currently change treatment or show a benefit for people with ALS.
Limitations and context
The report is a preprint rather than a completed peer-reviewed publication. It studied postmortem frontal-cortex tissue from people with C9ORF72-related FTD and induced pluripotent stem cell-derived cortical neurons, not people receiving a treatment. The findings therefore need confirmation and do not establish that these changes cause ALS or predict clinical outcomes.