SNPs in Aβ clearance proteins Lower CSF Aβ1-42 levels and earlier onset of dementia in PD

Objective: To evaluate whether genetic variants in beta-amyloid (A beta) clearance proteins are associated with CSF levels of A beta(1-42) on a biological level and the onset of dementia on a clinical level in Parkinson disease (PD). Methods: We analyzed genetic variants known to be involved in A beta clearance in a PD group comprising 456 patients, 103 of them with dementia. Single nucleotide polymorphisms in the genes APOE, cystatin C (CST), and membrane metalloendopeptidase (MME) were evaluated in relation to demographic variables, clinical phenotypes, and CSF A beta(1-42) levels using a crosssectional approach. Results: Risk variants in the genes APOE and CST were associated with lower CSF A beta(1-42) levels. Clinically, patients with 2 risk alleles in CST tended to show a shorter interval from age at onset of PD to age at onset of dementia. Conclusions: This study suggests that genetic variants associated with A beta clearance are involved in the pathogenesis of dementia in PD and possibly influence the onset of dementia.