Sex-Specific Patterns of Taste Dysfunction, Their Relationships with α-Synuclein Profiling, and Supervised Learning-Based Diagnosis in Parkinson’s Disease (PD)

Taste impairment is a little-known non-motor Parkinson's disease (PD) feature with potential diagnostic value. However, its biological basis and sex-specific patterns remain unclear. We combined psychophysical taste testing, salivary α synuclein (αsyn) profiling, genotyping of four SNCA polymorphisms, and Supervised Learning (SL) within a unified, sex-aware analytical framework to analyze sensory, molecular, and genetic correlates of gustatory dysfunction in 99 PD patients and 60 healthy controls. Overall taste identification was markedly reduced in PD, independently of sex. However, males and females showed distinct taste quality alterations: females preserved sour recognition, while males showed marked citric acid misidentification. SL modeling achieved high accuracy, revealing that the inability to perceive saltiness was most informative overall, astringency misidentification strongly predicted female PD, and sour misidentification characterized male PD. Salivary oligomeric αsyn showed a significant sex × diagnosis interaction, being elevated only in PD females, specifically those failing to identify astringency. Genotype-phenotype analyses revealed sex-dependent associations between SNCA variants (rs356219, rs181489, and rs2583988) and astringency recognition. These findings demonstrated that sex critically shapes the interplay between taste dysfunction, peripheral αsyn biology, and SNCA genetics in PD, supporting sex-aware chemosensory phenotyping and the development of precision taste-based biomarkers.