BACKGROUND

A number of genetic variants have previously been identified and associated with the risk of Alzheimer's disease (AD), including rs10838725 in CELF1, rs28834970 in PTK2B, rs17125944 in FERMT2, and rs10410544 in SIRT2 based on genome-wide association studies. Considering the overlap between the clinical manifestation and pathological characteristics of AD and Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), we conducted a large sample study to investigate the associations between these variants and these three common neurodegenerative diseases in a Chinese population.

METHODS

A total of 2449 patients, including 1219 PD, 870 sporadic ALS, and 360 MSA, and 821 healthy controls were examined for this study. All cases were genotyped for single-nucleotide polymorphisms using Sequenom iPLEX assay technology.

RESULTS

No significant differences were found in genotype distribution and minor allele frequencies between the four candidate variants and the three neurodegenerative diseases. However, a significant difference was found in the minor allele frequency of rs28834970 in PTK2B between PD patients with normal and abnormal cognitive function (p = 0.001). Moreover, the minor allele "C" was associated with an increased risk for cognitive impairment in PD (OR = 1.84). Although this observation was not significant (p = 0.064), the mean Addenbrooke's Cognitive Examination-Revised (ACER) score of PD patients with the risk allele of rs28834970 was 2.913 ± 1.569 points lower than that of PD patients without the risk allele.

CONCLUSIONS

This study provides new insight into some of the phenotypes that may share the common pathogenesis of different neurodegenerative diseases.