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

Surfen and oxalyl surfen decrease tau hyperphosphorylation and mitigate neuron deficits in vivo in a zebrafish model of tauopathy
ConclusionOur findings demonstrate for the first time that surfen, a well-tolerated molecule in clinical settings, and its derivative, oxalyl surfen, could mitigate or delay neuronal defects in tauopathies, including Alzheimer ’s disease. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 16, 2018 Category: Neurology Source Type: research

The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms
AbstractNearly 30% of adults 40  years and older in the United States are on a statin. Their widespread use heightens the importance of careful consideration of their varied effects on the body. Although randomized controlled trials have not confirmed cognitive impairing effects with statins, continuing evidence suggests statins have the ability to cause reversible cognitive impairment in some patients. Paradoxically, statins have also been shown to decrease the risk of dementia, Alzheimer’s disease, and improve cognitive impairment in some cases. However, randomized controlled trials have similarly failed to fi...
Source: Translational Neurodegeneration - February 27, 2018 Category: Neurology Source Type: research

Factors that influence adult neurogenesis as potential therapy
AbstractAdult neurogenesis involves persistent proliferative neuroprogenitor populations that reside within distinct regions of the brain. This phenomenon was first described over 50 years ago and it is now firmly established that new neurons are continually generated in distinct regions of the adult brain. The potential of enhancing the neurogenic process lies in improved brain cognition and neuronal plasticity particularly in the context of neuronal injury and neurodegenerative disorders. In addition, adult neurogenesis might also play a role in mood and affective disorders. The factors that regulate adult neurogenesis h...
Source: Translational Neurodegeneration - February 21, 2018 Category: Neurology Source Type: research

Hydrogen sulfide, nitric oxide, and neurodegenerative disorders
AbstractHydrogen Sulfide (H2S) and Nitric Oxide (NO) have become recognized as important gaseous signaling molecules with enormous pharmacological effects, therapeutic value, and central physiological roles. NO is one of the most important regulators of the pathophysiological condition in central nervous system (CNS). It is critical in the various functioning of the brain; however, beyond certain concentration/level, it is toxic. H2S was regarded as toxic gas with the smell like rotten egg. But, it is now regarded as emerging neuroprotectant and neuromodulator. Recently, the use of donors and inhibitors of these signaling ...
Source: Translational Neurodegeneration - February 13, 2018 Category: Neurology Source Type: research

Alzheimer ’s disease hypothesis and related therapies
AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disorder and the most common cause for dementia. There are many hypotheses about AD, including abnormal deposit of amyloid β (Aβ) protein in the extracellular spaces of neurons, formation of twisted fibers of tau proteins inside neurons, choline rgic neuron damage, inflammation, oxidative stress, etc., and many anti-AD drugs based on these hypotheses have been developed. In this review, we will discuss the existing and emerging hypothesis and related therapies. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 30, 2018 Category: Neurology Source Type: research

AGE-induced neuronal cell death is enhanced in G2019S LRRK2 mutation with increased RAGE expression
ConclusionsThese data suggest that enhanced AGE-RAGE interaction contributes to LRRK2 G2019S mutation-mediated progressive neuronal loss in PD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 23, 2018 Category: Neurology Source Type: research

Clinical features of Parkinson ’s disease with and without rapid eye movement sleep behavior disorder
ConclusionpRBD+ PD patients exhibited greater changes in non-motor symptoms. However, there was no increase in motor deficits. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 21, 2017 Category: Neurology Source Type: research