SNPs in Aβ clearance proteins: Lower CSF Aβ1-42 levels and earlier onset of dementia in PD
To evaluate whether genetic variants in β-amyloid (Aβ) clearance proteins are associated with CSF levels of Aβ1-42 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 Aβ 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 Aβ1-42 levels using a cross-sectional approach.Results:
Risk variants in the genes APOE and CST were associated with lower CSF Aβ1-42 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 Aβ clearance are involved in the pathogenesis of dementia in PD and possibly influence the onset of dementia.