This Italian case-control study examined whether three AQP4 gene polymorphisms were associated with Parkinson’s disease (PD) risk or specific nonmotor symptoms. Researchers genotyped 380 people with idiopathic PD and 461 age- and sex-matched healthy controls for AQP4 single nucleotide polymorphisms (SNPs) rs2075575, rs162009, and rs335929. Overall, none of the three SNPs were associated with PD risk, and haplotype analysis also showed no association with PD susceptibility. Mini-Mental State Examination scores and age at PD onset were not meaningfully influenced by the analyzed SNPs.
However, the study found potential associations between specific AQP4 variants and nonmotor symptoms in patients with PD. The rs162009 AA genotype appeared to be associated with lower likelihood of REM sleep behavior disorder, while the rs2075575 GA genotype was associated with higher likelihood of hallucinations; the AA genotype appeared protective. The authors suggest these findings may point to a possible role for AQP4 and glymphatic system function in PD-related sleep and psychiatric symptoms, but they emphasize that the results are preliminary and require replication in larger cohorts with more rigorous assessment of REM sleep behavior disorder and hallucinations.
Reference: Agliardi C, Guerini FR, Zanzottera M, et al. Analysis of AQP4 SNPs and Their Association With REM Sleep Behavior Disorder and Hallucinations in Parkinson’s Disease. Mol Neurobiol. 2025 Dec 16;63(1):302. doi: 10.1007/s12035-025-05495-z.
