Progranulin Gene Mutations and Inflammation in Frontotemporal Dementia
Author Information
Author(s): Bossù Paola, Salani Francesca, Alberici Antonella, Archetti Silvana, Bellelli Giuseppe, Galimberti Daniela, Scarpini Elio, Spalletta Gianfranco, Caltagirone Carlo, Padovani Alessandro, Borroni Barbara
Primary Institution: IRCCS Santa Lucia Foundation
Hypothesis
Loss of function mutations in the progranulin gene are related to pro-inflammatory cytokine dysregulation in frontotemporal lobar degeneration patients.
Conclusion
The profile of circulating pro-inflammatory cytokines is altered in symptomatic FTLD patients with PGRN mutations, suggesting IL-6 as a potential therapeutic target.
Supporting Evidence
- Circulating IL-6 is increased in PGRN-mutated FTLD patients compared to non-mutated patients and controls.
- TNF-α and IL-18 levels did not differ among the groups.
- Asymptomatic PGRN mutation carriers did not show altered IL-6 levels.
Takeaway
People with a specific gene mutation related to a brain disease have higher levels of a certain inflammatory substance in their blood when they show symptoms, which might help us find new treatments.
Methodology
Serum levels of IL-6, TNF-α, and IL-18 were analyzed in FTLD patients with and without PGRN mutations.
Potential Biases
Potential bias due to small sample size and lack of diverse demographic representation.
Limitations
The number of subjects with PGRN mutations is low, and results need replication in larger samples.
Participant Demographics
92 FTLD patients (78 without PGRN mutations, 14 with PGRN mutations) and 59 healthy controls.
Statistical Information
P-Value
p<0.001 for IL-6 levels between FTLD PGRN+ and FTLD PGRN- patients.
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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