MicroRNAs (miRNAs) are endogenous small (18–25 nt), single-stranded, non-coding RNAs that play key roles in post-transcriptional gene expression regulation. The expression profiles of miRNAs in biofluids and tissues change in various diseases. Multiple system atrophy (MSA) and Parkinson’s disease (PD) are both categorized as α-synucleinopathies and often present with similar clinical manifestations. This study aimed to identify miRNAs that are differently expressed in plasma samples of PD patients, MSA patients, and healthy controls. We used microarray analysis to screen for miRNAs that are up- and down-regulated in these patients and analyzed the relative-quantitative expression levels of the identified miRNAs by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Hsa-miR-671-5p, hsa-miR-19b-3p, and hsa-miR-24-3p showed significantly different expression levels among patients with MSA-C, MSA-P, or PD, and healthy controls. Hsa-miR-671-5p levels were lower in the MSA-P and PD than the MSA-C and control groups, hsa-miR-19b-3p levels were higher in the PD than the other groups, and hsa-miR-24-3p levels were higher in the PD than the MSA-C group. Hsa-miR-671-5p was the first miRNA shown to be expressed differently between MSA-C and MSA-P in plasma. Interestingly, the expression levels of hsa-miR-19b-3p and hsa-miR-24-3p were positively correlated, indicating that these miRNAs may be involved in the same processes in PD pathogenesis. Our findings suggest that hsa-miR-671-5p, hsa-miR-19b-3p, and hsa-miR-24-3p may reflect the pathophysiology or symptoms of PD and MSA. Electronic supplementary material The online version of this article (10.1186/s13041-019-0471-2) contains supplementary material, which is available to authorized users.

Correspondence to Hidenao Sasaki, h-isasak@med.hokudai.ac.jp Although there are various types of biomarkers such as molecular markers and imaging markers, an appropriate maker for neurodegenerative disease has not been identified. Thus, we use clinical evaluation scales. However, it is important to identify an appropriate biomarker in order to evaluate the efficiency of a given clinical trial.Here, we performed gait analyses in patients with pure cerebellar type spinocerebellar degeneration (SCD) and assessed whether the obtained data could be used as a neurophysiological biomarker for cerebellar ataxia.Here we performed gait analysis in patients with pure cerebellar type spinocerebellar degeneration (SCD) and assessed whether the obtained data could be used as a neurophysiological biomarker for cerebellar ataxia. We evaluated the clinical severity of each patient in the SCD group using the Scale for the Assessment and Rating of Ataxia (SARA) [1, 2] and the Berg Balance Scale (BBS) [3,4]. The mean SARA of the SCD group was 13.26±4.43, while the mean Unified Parkinson's Disease Rating Scale (UPDRS) part III was 18. 48±8.4760. 6 This study was approved by the ethics panels of Hokkaido University Hospital and Kushiro Rosai Hospital. Methods (Fig. 1)Acceleration signals were measured during 6 min walking and 1 min standing tasks by two sets of triaxial accelerometers (Mimamori-gait system, LSI Medience; size, 7.5 cm × 5 cm × 2 cm; weight, 95 g) that were secured with a fixation vest to the middle of the subject's lower and upper back.When in the standing position, the subjects were evaluated with their eyes open for 1 min and then their eyes closed for another 1 min. An assistant remained beside the subjects in order to prevent falls, however, no falls occurred. The subjects were evaluated while they shuttle-walked a 30 m straight line for 6 min (6-min walk test (6MWT) [5]). Similar tasks were performed in the JASMITT study [6] and in other studies. When standing in the anatomical position, the orientation of the three acceleration axes, X, Y, and Z, were medial/lateral (ML), vertical (VT), and anterior/posterior (AP), respectively. Data were collected at a sampling frequency of 100 Hz and stored on a secure digital memory card inserted into the device for later analysis. To quantify body motion during standing, we examined parameters as follows:1. The three acceleration components ax(t), ay(t), and az(t) were smoothed by a moving-window average with a window size of 5.6 s to generate three 8 baseline signals: Bx(t), By(t), and Bz(t). Statistical analysisWe used Student's t-test for inter-group comparison and Pearson's correlation coefficients for disease severity and each parameter analysis.The JMPⓇ Pro 11.2.0 software program (SAS Institute Inc., Cary, NC, USA) was used for statistical analyses. We considered the results significant if p<0.05. The test of significance was adjusted for multiple testing using a Bonferroni step-down (Holm) correction. ResultsWe compared each parameter of SCD patients to that of...

Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those of individuals with multiple system atrophy and Alzheimer’s disease. The neuropathological findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral degeneration and hippocampal sclerosis. Whole-exome analysis of this family identified a novel missense mutation in BSN. Within the pedigree, the detected BSN mutation was found only in affected individuals. Further genetic analyses were conducted in probands from four other pedigrees with PSP-like syndrome and in 41 sporadic cases. Three missense mutations in BSN that are very rarely listed in databases of healthy subjects were found in four sporadic cases. Western blot analysis of tau following the overexpression of wild-type or mutated BSN revealed the possibility that wild-type BSN reduced tau accumulation, while mutated BSN lost this function. An association between BSN and neurological diseases has not been previously reported. Our results revealed that the neurodegenerative disorder associated with the original proband’s pedigree is a novel tauopathy, differing from known dementia and parkinsonism syndromes, including PSP.

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Image findings of BRONJ were characterized as a severe sclerotic change combined with osteolysis, sequestration, periosteal reaction and spread of soft tissue inflammation around the jaws.