Sex differences modulate the serum metabolome profiles in Parkinson’s disease patients harbouring pathogenic mutations in GBA1, LRRK2, TMEM175, PARK2, PINK1, and PARK7 genes

ABSTRACT:

Background: Sex and genetic background have an impact on Parkinson’s disease (PD) insurgence, but the comprehension of how these factors affect the circulating profile of PD patients is still an aim of study.

Objectives: In this study we aimed to investigate whether genetic background and sex could highlight specific alteration at circulating level in the serum metabolome of PD patients stratified for gender carrying the most common pathogenic mutations in LRRK2, PINK1, PARK2, PARK7, TMEM175 and GBA1.

Methods: We applied an untargeted ¹H NMR-based analysis in serum samples of genetics PD patients (n=119) and sex-age matched controls (n=48). Specifically, we selected 17 LRRK2 carriers (F=11, M=6), 40 PINK1-PARK2-PARK7 carriers (F=18, M=22), 32 TMEM175 carriers (F= 12, M= 20) and 30 GBA1 carriers (F=17, M=13).

Results: Our results disclosed a different metabolomic signature between male and female PD patients, sustaining the hypothesis of a different impact of the disease across the two genders. Serum metabolomic analysis highlighted specific deregulated pathways based on genetic background and sex within PD patients groups. In particular, we demonstrated altered Folate, Glycine, Serine and Nicotinate and nicotamide metabolism in males TMEM175, GBA1, PARK2/PINK1/PARK7 and LRRK2 carriers, respectively. Conversely, across the female groups TMEM175, LRRK2 and PARK2/PIK1/PARK7 carriers showed specific alteration in Spermidine and spermine biosynthesis, Cystein and Ketone body metabolism, respectively. Interestingly, without considering the genetic background, males PD patients shared a higher number of impaired pathways, including amino acids metabolism, bioenergetic processes and antioxidant molecules production, when compared to the female ones whose shared alteration is represented  by deregulated lipid pathways. 

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

PROVIDER: MTBLS12753 | MetaboLights | 2026-06-26

REPOSITORIES: MetaboLights