SNPs in Aß clearance proteins: Lower CSF Aß1-42 levels and earlier onset of dementia in PD.

OBJECTIVE: To evaluate whether genetic variants in ß-amyloid (Aß) clearance proteins are associated with CSF levels of Aß1-42 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 Aß 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 Aß1-42 levels using a cross-sectional approach. RESULTS: Risk variants in the genes APOE and CST were associated with lower CSF Aß1-42 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 Aß clearance are involved in the pathogenesis of dementia in PD and possibly influence the onset of dementia.

Comparable autoantibody serum levels against amyloid- and inflammation-associated proteins in Parkinson's disease patients and controls.

Naturally occurring autoantibodies (NAbs) against a number of potentially disease-associated cellular proteins, including Amyloid-beta1-42 (Abeta1-42), Alpha-synuclein (Asyn), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and S100 calcium binding protein B (S100B) have been suggested to be associated with neurodegenerative disorders, in particular Alzheimer's (AD) and Parkinson's disease (PD). Whereas the (reduced) occurrence of specific NAbs in AD is widely accepted, previous literature examining the relation of these NAb titres between PD patients and controls, as well as comparing these levels with demographic and clinical parameters in PD patients have produced inconsistent findings. We therefore aimed, in a cross-sectional approach, to determine serum titres of the above NAbs in a cohort of 93 PD patients (31 of them demented) and 194 controls. Levels were correlated with demographic and clinical variables, cerebrospinal fluid Abeta1-42, total tau and phospho-tau levels, as well as with single nucleotide polymorphisms (SNPs) of genes which either have been reported to influence the immune system, the amyloid cascade or the occurrence of PD (ApoE, GSK3B, HLA-DRA, HSPA5, SNCA, and STK39). The investigated NAb titres were neither significantly associated with the occurrence of PD, nor with demographic and clinical parameters, neurodegenerative markers or genetic variables. These results argue against a major potential of blood-borne parameters of the adaptive immune system to serve as trait or state markers in PD.