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Author Spotlight: Exploring Sex-Specific Glial Signatures and Therapeutic Leads for Alzheimer's Disease
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Sex differences in brain protein expression and disease.
Aliza P Wingo1,2, Yue Liu3, Ekaterina S Gerasimov3
1Veterans Affairs Atlanta Health Care System, Decatur, GA, USA. aliza.wingo@emory.edu.
Nature Medicine
|August 31, 2023
Summary
Biological sex significantly impacts human brain protein levels and their genetic regulation. This study reveals sex-differentiated protein abundance and sex-biased genetic effects, offering insights into sex differences in brain function and disease.
Area of Science:
- Neuroscience
- Genetics
- Proteomics
Background:
- Complex human traits exhibit sex differences, yet the underlying molecular mechanisms remain largely unknown.
- Understanding sex-specific biological processes is crucial for personalized medicine and disease treatment.
Purpose of the Study:
- To investigate the influence of biological sex on protein expression in the human brain.
- To explore the genetic regulation of sex-differentiated protein abundance and its implications for brain traits and diseases.
Main Methods:
- Analysis of 1,277 human brain proteomes to identify sex-differentiated protein abundance.
- Identification of sex-biased protein quantitative trait loci (sb-pQTLs) to understand genetic regulation.
- Integration of protein quantitative trait loci (pQTLs) with sex-stratified genome-wide association studies (GWAS).
Main Results:
- 13.2% of brain proteins showed sex-differentiated abundance, and 1.5% had sb-pQTLs.
- Sex effects on genetic regulation were more pronounced at the protein level than the transcript level.
- An average of 25% of genes for psychiatric and neurologic traits had sex-differentiated protein abundance, with 12 proteins showing sb-pQTLs.
Conclusions:
- Biological sex plays a significant role in human brain proteome and its genetic regulation.
- These findings provide novel insights into the molecular mechanisms driving sex differences in brain function and disease susceptibility.
- The study highlights the importance of sex-specific analyses in understanding complex traits and neurological disorders.
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