Proteome-wide Mendelian randomization identifies causal plasma proteins in frontotemporal dementia
1Department of Cardiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, 18th, Section 3, Renmin Road South, Wuhou District, Chengdu, Sichuan, 610041, China.
Summary
This study identified specific plasma proteins linked to frontotemporal dementia (FTD) risk and progression. These proteins may serve as future biomarkers and therapeutic targets for FTD subtypes.
Area of Science:
- Neuroscience
- Genetics
- Proteomics
Background:
- Frontotemporal dementia (FTD) is a complex neurodegenerative disorder lacking effective treatments.
- Plasma proteomic signatures are emerging as key indicators for understanding FTD mechanisms and developing interventions.
Purpose of the Study:
- To investigate causal links between plasma proteins and FTD, including its subtypes.
- To identify potential plasma protein biomarkers for FTD diagnosis and therapeutic targeting.
Main Methods:
- Protein-wide Mendelian randomization meta-analysis was employed.
- Comprehensive datasets of protein quantitative trait loci were utilized to explore genetic associations.
Main Results:
- Four plasma proteins (RGS7, ASAP2, TMCC3, VPS29) were significantly associated with FTD.
- Distinct protein signatures were observed across FTD subtypes, including behavioral variant FTD, FTD overlapping with motor neuron disease, progressive non-fluent aphasia, and semantic dementia.
Conclusions:
- Specific plasma proteins play a role in FTD pathogenesis, with effects varying by subtype.
- The identified proteins hold potential as biomarkers for patient stratification and as targets for novel therapeutic strategies.
