Cerebrospinal fluid A42 levels and APP processing pathway genes in Parkinson's disease

BackgroundOf recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (A), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF A(42) levels in Parkinson's disease (PD). MethodsParkinson's disease (n=86) and control (n=161) DNA were genotyped for 19 regulatory region tagging single-nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN, and APH1B) involved in the cleavage of APP. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE 4 status. ResultsSignificant correlation with CSF A(42) levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF A(42) levels in controls was observed for three SNPs (APP rs214484, rs2040273, and PSEN1 rs362344). ConclusionsIn addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF A(42) levels in APOE 4 noncarriers. Further hypotheses generated include that decreased CSF A(42) levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared with other neurodegenerative diseases, such as AD, are warranted. (c) 2015 International Parkinson and Movement Disorder Society