Alzheimer's disease susceptibility genes modify the risk of Parkinson disease and Parkinson's disease-associated cognitive impairment.

The pathogenic mechanism underlying Parkinson's disease (PD) and PD- Cognitive impairment (CI) remains elusive. Its potential link to the risk factors in Alzheimer's disease (AD) is unclear. In this study, we analyzed 16 CE-associated single nucleotide polymorphisms (SNPs) in twelve genes in a Chinese cohort of 450 PD cases and 449 controls. Among our 298 cases clinically evaluated for CI, 113 cases did not show CI signs (PD-NC), 86 cases had mildly cognitive impairment (PD-MCI) and 99 cases had dementia (PD-D). We found that the APOE ε4 allele is associated with a higher risk for PD-D. Gene-gene interaction analysis revealed that three significant gene-gene interactions, including BDNF and CLU, APOE and CR1, and DYRK1A and CD2AP increase the risk for PD. Because these SNPs are known genetic risk factors for AD, their contribution to PD and PD-D shown in this study suggests that PD/PD-D and AD may share convergent pathways in their pathogenesis through gene-gene interactions.

Altered Functional Brain Connectomes between Sporadic and Familial Parkinson's Patients.

Familial Parkinson's disease (PD) is often caused by mutation of a certain gene, while sporadic PD is associated with variants of genes which can influence the susceptibility to PD. The goal of this study was to investigate the difference between the two forms of PD in terms of brain abnormalities using resting-state functional MRI and graph theory. Thirty-one familial PD patients and 36 sporadic PD patients underwent resting-state functional MRI scanning. Frequency-dependent functional connectivity was calculated for each subject using wavelet-based correlations of BOLD signal over 246 brain regions from Brainnetome Atlas. Graph theoretical analysis was then performed to analyze the topology of the functional network, and functional connectome differences were identified with a network-based statistical approach. Our results revealed a frequency-specific (0.016 and 0.031 Hz) connectome difference between familial and sporadic forms of PD, as indicated by an increase in assortativity and decrease in the nodal strength in the left medial amygdala of the familial PD group. In addition, the familial PD patients also showed a distinctive functional network between the left medial amygdala and regions related to retrieval of motion information. The present study indicates that the medial amygdala might be most vulnerable to both sporadic and familial PD. Our findings provide some new insights into disrupted resting-state functional connectomes between sporadic PD and familial PD.

Identifying the presence of Parkinson's disease using low-frequency fluctuations in BOLD signals.

Parkinson's disease (PD) is a chronic, progressive, and degenerative neurological disorder that is characterized by the degeneration of dopamine neurons in the substantia nigra and the formation of intracellular Lewy inclusion bodies. Resting-state functional magnetic resonance imaging (RS-fMRI) has demonstrated evidence of changes in metabolic patterns in individuals with PD. The purpose of this study was to determine whether the presence of PD could be "predicted" based on resting fluctuations in the blood oxygenation level dependent signal. We utilized RS-fMRI to measure the amplitude of low-frequency fluctuation (ALFF) and the fractional ALFF (fALFF) in 51 patients with PD and 50 age- and sex-matched healthy controls. Compared with the healthy controls, the individuals with PD exhibited altered ALFFs in the bilateral lingual gyrus and left putamen and an altered fALFF in the right cerebellum posterior lobe. Support vector machines (SVMs), which comprise a supervised pattern recognition method that enables predictions at the individual level, were trained to separate individuals with PD from healthy controls based on the ALFF and fALFF. Using the leave-one-out cross-validation method to analyze our sample, we reliably distinguished the participants with PD from the controls with 92% sensitivity and 87% specificity. Overall, these findings suggest that the SVM-neuroimaging approach may be of particular clinical value because it enables the accurate identification of PD at the individual level. RS-fMRI should be considered for development as a biomarker and an analytical tool for the evaluation of PD.

RAB39B gene mutations are not linked to familial Parkinson's disease in China.

Recently, RAB39B mutations were reported to be a causative factor in patients with Parkinson's disease (PD). To validate the role of RAB39B in familial PD, a total of 195 subjects consisting of 108 PD families with autosomal-dominant (AD) inheritance and 87 PD families with autosomal-recessive (AR) inheritance in the Chinese Han population from mainland China were included in this study. We did not identify any variants in the coding region or the exon-intron boundaries of the gene by Sanger sequencing method in the DNA samples of 180 patients (100 with AD and 80 with AR). Furthermore, we did not find any variants in the RAB39B gene when Whole-exome sequencing (WES) was applied to DNA samples from 15 patients (8 with AD and 7 with AR) for further genetic analysis. Additionally, when quantitative real-time PCR was used to exclude large rearrangement variants in these patients, we found no dosage mutations in RAB39B gene. Our results suggest that RAB39B mutation is very rare in familial PD and may not be a major cause of familial PD in the Chinese Han Population.