SNPs in Aβ clearance proteins: Lower CSF Aβ levels and earlier onset of dementia in PD.

Objective: To evaluate whether genetic variants in β-amyloid (Aβ) clearance proteins are associated with CSF levels of Aβ 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 Aβ clearance in a PD group comprising 456 patients, 103 of them with dementia. Single nucleotide polymorphisms in the genes , cystatin C (), and membrane metalloendopeptidase () were evaluated in relation to demographic variables, clinical phenotypes, and CSF Aβ levels using a cross-sectional approach.

Results: Risk variants in the genes and were associated with lower CSF Aβ levels. Clinically, patients with 2 risk alleles in 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 Aβ clearance are involved in the pathogenesis of dementia in PD and possibly influence the onset of dementia.