BackgroundParkinson’s disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD.MethodsChanges in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set").ResultsGene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. ConclusionsOur data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2058-3) contains supplementary material, which is available to authorized users.

DLB-AD+) and AD-negative group (DLB-AD-) based on this profile. Cross-sectional data on age, sex, extrapyramidal signs, MMSE, CAMcog, DAD, NPI and duration of disease were compared. Neuropsychological test scores were standardized and clustered into four cognitive domains (memory, executive functioning, attention and visuospatial abilities). Global cognitive decline was measured with the MMSE and linear mixed models were used to investigate the relationship with AD-profile. Results: A CSF AD-profile was found in 48 patients (40%). Patients in the DLB-AD+ group were older (71 vs. 66 years, p ¼0.002), more often female (27.1 vs. 9.7%, p ¼0.023) and performed worse on daily functioning (Median DAD-scores 61.5/100 vs. 84/100, p ¼0.02). There were no differences in MMSE, CAMcog, NPI, or duration of disease. After correction for age, sex and education, patients in the DLB-AD+ group performed worse on memory tasks (OR¼0.53, 95%CI 0.29-0.96, p ¼0.035). Linear mixed models with a mean follow-up of 2 years (range 1-6 years) showed a trend towards faster decline on the MMSE in the DLB-AD+ group. Conclusions: This study in a large, clinically well-characterised cohort of probable DLB patients showed that concomitant AD-pathology is associated with worse performance in daily functioning and worse memory function. Longitudinal data suggest faster cognitive decline. In addition to data from neuropathological studies, these results confirm that AD-pathology has relevant additional clinical effects in DLB. Background:The clinical diagnosis of dementia with Lewy bodies (DLB) is based on core and suggestive features. We set out to investigate whether dopamine transporter imaging using DaTSCANÔ would help in diagnosing DLB (by changing the diagnosis from possible DLB to probable DLB or non-DLB) and to identify which core and suggestive features would most be associated with a follow-up diagnosis of probable DLB. Methods: 187 patients with possible DLB were recruited from 21 centres in 6 European countries. Patients were randomized to have a DaTSCANÔ (n¼127) or to have no imaging (Control group, n¼60). The proportion of patients with changes in clinical diagnosis was assessed in terms of DLB features at baseline and after obtaining DaTSCANÔ results. The evolution of features and diagnosis was compared at 8 and 24-weeks of follow-up. Results: 170 subjects were considered valid for the primary endpoint assessment. Overall prevalence of DLB features was similar between the two study groups. Parkinsonism was the most frequent DLB feature (29%), followed by fluctuations (28%), hallucinations (24%) and REM sleep behaviour disorders (17%). No patients reported neuroleptic sensitivity.More patients in the DaTSCANÔ group had a change in diagnostic category after 8 weeks (61% vs 4%; P<.0001) while at 24-weeks there continued to be a major difference between the two groups (71 vs 16% p<0.0001).Parkinsonism at baseline was more prevalent in probable DLB and was the only feature that evolved at 6-months follow-up particularly in patients with fin...

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