Constipation, deficit in colon contractions and alpha-synuclein inclusions within the colon precede motor abnormalities and neurodegeneration in the central nervous system in a mouse model of alpha-synucleinopathy
ConclusionsGastrointestinal dysfunction in A53T αS mice represents an early sign of αS-driven pathology without concomitant CNS involvement. We believe that this model can be very useful to study disease-modifying strategies that could extend the prodromal phase of PD and halt αS pathology from reaching the brain. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 6, 2019 Category: Neurology Source Type: research

Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson ’s disease
AbstractParkinson ’s disease (PD) is the most common neurodegenerative movement disorder, which is characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta concomitant with Lewy body formation in affected brain areas. The detailed pathogenic mechanisms underlying the selec tive loss of dopaminergic neurons in PD are unclear, and no drugs or treatments have been developed to alleviate progressive dopaminergic neuron degeneration in PD. However, the formation of α-synuclein-positive protein aggregates in Lewy body has been identified as a common pathological feature of P...
Source: Translational Neurodegeneration - February 4, 2019 Category: Neurology Source Type: research

Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer ’s disease
AbstractBackgroundSerotoninergic pathways underlying delusion symptoms in Alzheimer ’s disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription.MethodsWe investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer ’s Association criteria. All participants underwent a comprehensive evaluation with a standardized compr...
Source: Translational Neurodegeneration - February 1, 2019 Category: Neurology Source Type: research

Suppression of astrocytic autophagy by αB-crystallin contributes to α-synuclein inclusion formation
ConclusionsThis study reveals a novel function for CRYAB as a natural inhibitor of astrocytic autophagy and shows  that knockdown of CYRAB may provide a therapeutic target against proteinopathies such as synucleinopathies. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 18, 2019 Category: Neurology Source Type: research

Better survival in female SOD1 -mutant patients with ALS: a study of SOD1 -related natural history
ConclusionsThe results highlight a distinct mutational distribution and natural history spectrum in ALS patients carryingSOD1 mutations in China. A prominent mild disease progression was observed in female patients, which had rarely been reported in the previous literature. This finding, together with the detailed analysis of natural history among each mutation, can have important implications for future genetic counselling andSOD1-targeted clinical trials. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 8, 2019 Category: Neurology Source Type: research

Transcranial direct current stimulation enhances theory of mind in Parkinson ’s disease patients with mild cognitive impairment: a randomized, double-blind, sham-controlled study
ConclusionsWe show for the first time that active tDCS over the MFC enhances ToM in patients with PD-MCI, and suggest that non-invasive brain stimulation could be used to ameliorate ToM deficits observed in these patients. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 7, 2019 Category: Neurology Source Type: research

Amyloid, tau, pathogen infection and antimicrobial protection in Alzheimer ’s disease –conformist, nonconformist, and realistic prospects for AD pathogenesis
ConclusionAD is a multi-factor complex disorder, which likely requires a combinatorial therapeutic approach to successfully slow or reduce symptomatic memory decline. A better understanding of how various causal and/or risk factors affecting disease onset and progression will enhance the likelihood of conceiving effective treatment paradigms, which may involve personalized treatment strategies for individual patients at varying stages of disease progression. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 24, 2018 Category: Neurology Source Type: research

Correction to: Alterations of brain local functional connectivity in amnestic mild cognitive impairment
In the original publication of this article [1] surname of the first author is wrong. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 24, 2018 Category: Neurology Source Type: research

Dynamic changes of CX3CL1/CX3CR1 axis during microglial activation and motor neuron loss in the spinal cord of ALS mouse model
ConclusionsOur data revealed the dynamic changes of CX3CL1/CX3CR1 axis and an imbalanced M1/M2 microglial activation during ALS pathological progression. These findings may help identify potential molecular targets for ALS therapy. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 21, 2018 Category: Neurology Source Type: research

Efficacy and safety of rasagiline in Chinese patients with early Parkinson ’s disease: a randomized, double-blind, parallel, placebo-controlled, fixed-dose study
ConclusionsRasagiline is effective, safe, and well tolerated as monotherapy for the treatment of Chinese PD patients.Trial registrationClinicaltrials.gov:NCT01556165. Registered 13 Mar 2012. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 6, 2018 Category: Neurology Source Type: research

Rare TBK1 variants in patients with frontotemporal dementia and amyotrophic lateral sclerosis in a Chinese cohort
ConclusionsThis study enlarges the genetic and phenotypic spectrum ofTBK1 mutation in a Chinese cohort. Our data indicates thatTBK1 mutation is not a common cause for ALS and FTD in Chinese patients. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 4, 2018 Category: Neurology Source Type: research

GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis
This study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following GM6 treatment (6, 24 and 48  h).ResultsWe identified 2867 protein-coding genes with expression significantly altered by GM6 (FDR  
Source: Translational Neurodegeneration - December 3, 2018 Category: Neurology Source Type: research

Alterations of brain local functional connectivity in amnestic mild cognitive impairment
ConclusionsThis study provides provisional evidence that aMCI is associated with abnormal ReHo within the DMN, executive control network, visual network, and sensorimotor network. These local functional connectivity alterations suggest coexistence of functional deficits and compensation in these networks. These findings contribute to the modeling of brain functional connectomes and to a better understanding of the neural substrates of aMCI. Confounding factors merit much attention and warrant future investigations. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - November 7, 2018 Category: Neurology Source Type: research

Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome
DiscussionThese findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis, thus ultimately resulting in improved cognition. Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - November 6, 2018 Category: Neurology Source Type: research

Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons
ConclusionsOur studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs. Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - November 5, 2018 Category: Neurology Source Type: research

Aberrant functional connectivity network in subjective memory complaint individuals relates to pathological biomarkers
ConclusionWe found impaired local, but not global, intrinsic connectivity networks in SMC individuals. Given the relationships between DC value and tau level, we hypothesized that functional changes in SMC individuals might relate to pathological biomarkers. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - October 19, 2018 Category: Neurology Source Type: research

Neurodegeneration-associated FUS is a novel regulator of circadian gene expression
ConclusionsTherefore, we have demonstrated FUS as a modulator of circadian gene expression, and provided novel mechanistic insights into the mutual influence between circadian control and neurodegeneration-associated proteins. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - October 12, 2018 Category: Neurology Source Type: research

CSF A β 1–42 level is associated with cognitive decline in early Parkinson’s disease with rapid eye movement sleep behavior disorder
ConclusionThese findings indicate that CSF A β1 –42 level is associated with global cognitive decline in early PD with RBD. The addition of CSF A β1 –42 to RBD testing increase the likelihood of identifying those at high risk for cognitive decline in early PD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - October 8, 2018 Category: Neurology Source Type: research

Alpha-synuclein overexpression in the olfactory bulb initiates prodromal symptoms and pathology of Parkinson ’s disease
ConclusionsThese results demonstrate that expression of exogenous mutant α-syn in the OB induces pathological changes in the sensitive brain fields by transferring pathogenic α-syn to adjacent fields. This method may be useful for establishing an animal model of prodromal PD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - September 28, 2018 Category: Neurology Source Type: research

Bis(9)-( −)-Meptazinol, a novel dual-binding AChE inhibitor, rescues cognitive deficits and pathological changes in APP/PS1 transgenic mice
ConclusionThese results indicate that B9M appears to have potential as an effective AChE inhibitor for the treatment of AD with symptom-relieving and disease-modifying properties. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - September 11, 2018 Category: Neurology Source Type: research

Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer ’s disease
AbstractBackgroundVisinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively. Phosphorylated tau (p-tau) reflects the neuropathology of Alzheimer ’s disease (AD) and is useful as diagnostic markers for AD. However, it is unknown whether these biomarkers have similar or complementary information in AD.MethodsWe stratified 121 participants from the Alzheimer ’s Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN), stable mild cognitive impairm...
Source: Translational Neurodegeneration - September 10, 2018 Category: Neurology Source Type: research

Dopaminergic neurons show increased low-molecular-mass protein 7 activity induced by 6-hydroxydopamine in vitro and in vivo
ConclusionTaken together, our data suggest that β5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - August 17, 2018 Category: Neurology Source Type: research

Objective assessment of bradykinesia in Parkinson ’s disease using evolutionary algorithms: clinical validation
ConclusionsOur study demonstrated that a simple to use device employing classifiers derived from EAs could not only be used to accurately measure different severity of bradykinesia in PD, but also had the potential to differentiate early stage PD from normality. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - August 16, 2018 Category: Neurology Source Type: research

Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice
ConclusionsThese findings suggest that the combination of ultra-high field diffusion MRI with fluorescent ALS mice reporters is a useful approach to detect and characterize presymptomatic white matter micro-ultrastructural changes and axonal connectivity anomalies in ALS. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - August 8, 2018 Category: Neurology Source Type: research

Properties of oscillatory neuronal activity in the basal ganglia and thalamus in patients with Parkinson ’s disease
This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.MethodsTwenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus (STN) DBS (n = 11), unilateral pallidotomy (n = 9) and unilateral thalamotomy (n = 9) were studied. Microelectrode recordings in the STN, globus pallidus internus (GPi) and ventral oral posterior/ventral intermediate of thalamus (Vop/Vim) were performed. Electromyography of the contralateral limbs was recorded. Single unit characterist ic...
Source: Translational Neurodegeneration - July 25, 2018 Category: Neurology Source Type: research

The role of substantia nigra sonography in the differentiation of Parkinson ’s disease and multiple system atrophy
AbstractBackgroundThe differential diagnosis of Parkinson ’s disease (PD) and multiple system atrophy (MSA) remains a challenge, especially in the early stage. Here, we assessed the value of transcranial sonography (TCS) to discriminate non-tremor dominant (non-TD) PD from MSA with predominant parkinsonism (MSA-P).MethodsEighty-six MSA-P patients and 147 age and gender-matched non-TD PD patients who had appropriate temporal acoustic bone windows were included in this study. All the patients were followed up for at least 2  years to confirm the initial diagnosis. Patients with at least one substantia nigra (SN) e...
Source: Translational Neurodegeneration - July 23, 2018 Category: Neurology Source Type: research

Cognitive characteristics in Chinese non-demented PD patients based on gender difference
ConclusionsCognitive impairments were common in PD patients even in the absence of dementia. PD patients with anti-parkinsonian medication had worse cognitive impairment than untreated patients. Genders may have different manifestations of cognitive impairment in PD patients. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - July 19, 2018 Category: Neurology Source Type: research

Adjunct rasagiline to treat Parkinson ’s disease with motor fluctuations: a randomized, double-blind study in China
This study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson’s disease, as a product registration study.MethodsThis 16-week, randomized, double-blind, parallel-group, multicenter, placebo-controlled study of rasagiline 1  mg/day included levodopa-treated patients with Parkinson’s disease and motor fluctuations. The primary efficacy endpoint was mean change from baseline in total daily OFF time over 16 weeks. Secondary endpoints were Clinical Global Impressions – Improvement (CGI-I), and change in Unified Parki nson’s Disease Rating Scal...
Source: Translational Neurodegeneration - June 30, 2018 Category: Neurology Source Type: research

Age-dependent alpha-synuclein accumulation and aggregation in the colon of a transgenic mouse model of Parkinson ’s disease
ConclusionsOur results show the development of α-syn pathology in the enteric neurons of the colon in a PD mouse model, which coincide with the appearance of motor deficits. Our mouse model possesses the potential and uniqueness for studying PD gastrointestinal dysfunction. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - June 30, 2018 Category: Neurology Source Type: research

Adjunct rasagiline to treat Parkinson ’s disease with motor fluctuations: a randomized, double-blind study in China
This study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson’s disease, as a product registration study.MethodsThis 16-week, randomized, double-blind, parallel-group, multicenter, placebo-controlled study of rasagiline 1  mg/day included levodopa-treated patients with Parkinson’s disease and motor fluctuations. The primary efficacy endpoint was mean change from baseline in total daily OFF time over 16 weeks. Secondary endpoints were Clinical Global Impressions – Improvement (CGI-I), and change in Unified Parki nson’s Disease Rating Scal...
Source: Translational Neurodegeneration - June 30, 2018 Category: Neurology Source Type: research

Age-dependent alpha-synuclein accumulation and aggregation in the colon of a transgenic mouse model of Parkinson ’s disease
ConclusionsOur results show the development of α-syn pathology in the enteric neurons of the colon in a PD mouse model, which coincide with the appearance of motor deficits. Our mouse model possesses the potential and uniqueness for studying PD gastrointestinal dysfunction. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - June 30, 2018 Category: Neurology Source Type: research

Impact of the biological definition of Alzheimer ’s disease using amyloid, tau and neurodegeneration (ATN): what about the role of vascular changes, inflammation, Lewy body pathology?
ConclusionResearch should aim at understanding the interaction between all these factors, rather than focusing on them individually. Hopefully this will lead to a personalized approach to the prevention of brain aging, based on individual biological, genetic and cognitive profiles. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - May 31, 2018 Category: Neurology Source Type: research

Chinese expert consensus on programming deep brain stimulation for patients with Parkinson ’s disease
ConclusionThis Chinese expert consensus on postoperative programming can standardize and improve postoperative management and programming of DBS for PD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - April 30, 2018 Category: Neurology Source Type: research

Divergent topological networks in Alzheimer ’s disease: a diffusion kurtosis imaging analysis
ConclusionsOur results suggest that DKI might be superior to DTI and could serve as a novel approach to understand the pathogenic mechanisms in neurodegenerative diseases. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - April 27, 2018 Category: Neurology Source Type: research

Cerebral glucose metabolic prediction from amnestic mild cognitive impairment to Alzheimer ’s dementia: a meta-analysis
AbstractBrain18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been utilized to monitor disease conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer ’s dementia (AD). However, the conversion patterns of FDG-PET metabolism across studies are not conclusive. We conducted a voxel-wise meta-analysis using Seed-basedd Mapping that included 10 baseline voxel-wise FDG-PET comparisons between 93 aMCI converters and 129 aMCI non-converters from nine longitudinal studies. The most robust and reliable metabolic alterations that predicted conversion from aMCI to AD were localized in the left pos...
Source: Translational Neurodegeneration - April 23, 2018 Category: Neurology Source Type: research

Treating refractory depression in Parkinson ’s disease: a meta-analysis of transcranial magnetic stimulation
ConclusionsAcross all but one study, rTMS appears to effectively reduce depression scores among self-reported and clinician administered inventories. The total weight average effect size showed that, when considering study sample sizes and degree of findings, this form of neurostimulation can relieve PD patients of their depressive symptoms. Further, rTMS is a promising alternative to traditional anti-depressant therapies when treating refractory depression in patients with PD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 22, 2018 Category: Neurology Source Type: research

Exercise-induced increase in brain-derived neurotrophic factor in human Parkinson's disease: a systematic review and meta-analysis
ConclusionsThis review provides preliminary evidence for the effectiveness of physical exercise treatments for persons with PD on BDNF blood levels. Further research is needed. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 20, 2018 Category: Neurology Source Type: research