Sex and subtype differences shape the blood metabolome profiles in Parkinson's disease.

ABSTRACT:

Rationale: Sex and type of Parkinson's disease (PD) significantly influence onset age, clinical manifestations, treatment response, disease progression and life expectancy. However, the selective influence of idiopathic and familial forms of PD in disrupting blood metabolome profiles across genders remains unclear.

Methods: We conducted an untargeted 1H NMR-based metabolomics study in a large cohort of clinically and genetically well-characterized patients and controls (n=385), which included: i) 56 women and 65 men diagnosed with idiopathic PD; ii) 60 women and 64 men with a familial form of PD; iii) 80 men and 60 women serving as healthy control groups.

Results: Multivariate Analysis (MVA) did not reveal differences in serum metabolomes between idiopathic and familial PD patients in both sexes. Similarly, MVA did not show significant variation among blood metabolomes of patients carrying distinct pathogenic variants, including LRRK2, TMEM175, PRKN, PINK1, PARK7 and GBA1. MVA indicates remarkable metabolome differences between idiopathic and familial subtypes compared to healthy controls. Notably, 1H NMR-based metabolomics unveiled a striking gender effect in influencing metabolome dysregulation across idiopathic or familial patients compared to matched controls. Specifically, our results indicate that amino acids, glutathione biosynthesis, energy homeostasis pathways, phospholipids and ketone body metabolism alterations are critically associated with the sex and genotype of PD individuals. However, regardless of the specific disease type, MVA consolidates the evidence that more pronounced blood metabolome dysregulations occurred in males than women with the same form of PD.

Conclusion: We reveal that men and women exhibit distinct serum metabolome dysregulations across idiopathic and familial forms of PD compared to healthy controls, further indicating the key role of gender and genetic background in controlling varying pathophysiological features of the disease.

INSTRUMENT(S): Nuclear Magnetic Resonance (NMR) -

PROVIDER: MTBLS11187 | MetaboLights | 2025-09-03

REPOSITORIES: MetaboLights