LAUSR

Objective: To evaluate whether genetic variants in &bgr;-amyloid (A&bgr;) clearance proteins are associated with CSF levels of A&bgr;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&bgr; 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&bgr;1-42 levels using a cross-sectional approach. Results: Risk variants in the genes APOE and CST were associated with lower CSF A&bgr;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&bgr; clearance are involved in the pathogenesis of dementia in PD and possibly influence the onset of dementia.