Search Our Scientific Publications & Authors

PLoS One 2019 18;14(4):e0215384. Epub 2019 Apr 18.

Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Research, Toronto Western Hospital, Toronto, Ontario, Canada.

Background: Successful patient-physician communication is critical for improving health outcomes, but research regarding optimal communication practices in Parkinson's disease is limited. The objective of the current study was to investigate barriers and facilitators of communication between persons with Parkinson's disease, carepartners, and physicians, specifically in the setting of off periods, with the goal of identifying ways to improve patient-carepartner-physician communication.

Method: We interviewed persons with Parkinson's, carepartners, and physicians (specialists and non-specialists) using a semi-structured questionnaire to identify and describe experiences, barriers, and facilitators relating to communication about off periods in Parkinson's disease. Read More

Nat Commun 2019 03 26;10(1):1371. Epub 2019 Mar 26.

Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.

Mitochondrial fragmentation and bioenergetic failure manifest in Huntington's disease (HD), a fatal neurodegenerative disease. The factors that couple mitochondrial fusion/fission with bioenergetics and their impacts on neurodegeneration however remain poorly understood. Our proteomic analysis identifies mitochondrial protein ATAD3A as an interactor of mitochondrial fission GTPase, Drp1, in HD. Read More

Tremor Other Hyperkinet Mov (N Y) 2019 4;9:601. Epub 2019 Feb 4.

Department of Neurology, University Hospital Zurich, Zurich, CH.

Background: Huntington's disease (HD) is a rare, progressive neurodegenerative disease. Currently, there is no cure for the disease, but treatment may alleviate HD symptoms. In recent years, several exercise training interventions have been conducted in HD patients. Read More

Nat Commun 2019 01 30;10(1):491. Epub 2019 Jan 30.

Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz, 78457, Konstanz, Germany.

The nematode Caenorhabditis elegans represents an important research model. Convenient methods for conditional induction of gene expression in this organism are not available. Here we describe tetracycline-dependent ribozymes as versatile RNA-based genetic switches in C. Read More

Mol Cell Neurosci 2019 03 24;95:43-50. Epub 2019 Jan 24.

Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder encoding a mutant form of the huntingtin protein (HTT). HD is pathologically characterized by loss of neurons in the striatum and cortex, which leads to progressive motor dysfunction, cognitive decline and behavioral symptoms. Stem cell-based therapy has emerged as a feasible therapeutic approach for the treatment of neurodegenerative diseases and may be effective in alleviating and/or halting the pathophysiological mechanisms underlying HD. Read More

Nat Med 2019 Feb 14;25(2):270-276. Epub 2019 Jan 14.

Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Vascular contributions to cognitive impairment are increasingly recognized as shown by neuropathological, neuroimaging, and cerebrospinal fluid biomarker studies. Moreover, small vessel disease of the brain has been estimated to contribute to approximately 50% of all dementias worldwide, including those caused by Alzheimer's disease (AD). Vascular changes in AD have been typically attributed to the vasoactive and/or vasculotoxic effects of amyloid-β (Aβ), and more recently tau. Read More

Alzheimers Dement 2019 01;15(1):158-167

Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Alzheimer's Disease Research Center, Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA. Electronic address:

Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Read More

Sensors (Basel) 2019 Jan 10;19(2). Epub 2019 Jan 10.

Laboratory of Images, Signals and Intelligent Systems (LISSI), University of Paris-Est Créteil (UPEC), 122 rue Paul Armangot, 94400 Vitry-Sur-Seine, France.

This article presents a machine learning methodology for diagnosing Parkinson's disease (PD) based on the use of vertical Ground Reaction Forces (vGRFs) data collected from the gait cycle. A classification engine assigns subjects to healthy or Parkinsonian classes. The diagnosis process involves four steps: data pre-processing, feature extraction and selection, data classification and performance evaluation. Read More

IEEE J Biomed Health Inform 2019 Jan 9. Epub 2019 Jan 9.

Background And Objective: New technology enables constant boost to the powers of mobile devices, which in the previous years have transformed from simple mobile phones to smart phones. Computational powers of these electronics enable actions that previously were possible only for computers. By the use of special applications we may benefit from sensors and multimedia capabilities of operating systems. Read More

eNeuro 2018 Nov-Dec;5(6). Epub 2018 Dec 21.

T.J. Watson IBM Research Center, Yorktown Heights, NY 10598.

Abnormal gamma band power across cortex and striatum is an important phenotype of Huntington's disease (HD) in both patients and animal models, but neither the origin nor the functional relevance of this phenotype is well understood. Here, we analyzed local field potential (LFP) activity in freely behaving, symptomatic R6/2 and Q175 mouse models and corresponding wild-type (WT) controls. We focused on periods of quiet rest, which show strong γ activity in HD mice. Read More

Tremor Other Hyperkinet Mov (N Y) 2018 26;8:604. Epub 2018 Oct 26.

Department of Neurology, National Neuroscience Centre, Cork University Hospital, Cork, IE.

Neuropsychologia 2019 01 26;122:116-124. Epub 2018 Oct 26.

Cognition and Brain Plasticity Unit, Neuroscience Program, IDIBELL (Institut d'Investigació Biomèdica de Bellvitge), L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address:

A cognitive stimulating lifestyle has been observed to confer cognitive benefits in multiple neurodegenerative diseases. However, the underlying neurobiological basis of this phenomenon remains unclear. Huntington's disease can provide a suitable model to study the effects and neural mechanisms of cognitive engagement in neurodegeneration. Read More

Nitric Oxide 2019 02 5;83:40-50. Epub 2018 Dec 5.

Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.

In Huntington's disease (HD), corticostriatal and striatopallidal projection neurons preferentially degenerate as a result of mutant huntingtin expression. Pathological deficits in nitric oxide (NO) signaling have also been reported in corticostriatal circuits in HD, however, the impact of age and sex on nitrergic transmission is not well characterized. Thus, we utilized NADPH-diaphorase (NADPH-d) histochemistry and qPCR assays to assess neuronal NO synthase (nNOS) activity/expression in aged male and female Q175 heterozygous mice. Read More

Open Biol 2018 12 5;8(12). Epub 2018 Dec 5.

PhD Program for Translational Medicine, China Medical University and Academia Sinica, Taiwan, Republic of China

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disease that is characterized by a triad of motor, psychiatric and cognitive impairments. There is still no effective therapy to delay or halt the disease progress. The striatum and cortex are two particularly affected brain regions that exhibit dense reciprocal excitatory glutamate and inhibitory gamma-amino butyric acid (GABA) connections. Read More

Handb Clin Neurol 2018 ;159:251-260

Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia. Electronic address:

Huntington disease (HD) is an autosomal-dominant, progressive, neurodegenerative disorder, characterized by involuntary movements and other motor impairments, cognitive/behavioral symptoms, and psychiatric disorders. Gait and balance impairments and falls greatly impact on the quality of life among people with HD, and being fall-prone is one of the strongest predictors of nursing-home placement. Gait impairment in HD is characterized by bradykinesia, reduced velocity, and increased variability in spatiotemporal features. Read More

Biochemistry (Mosc) 2018 Sep;83(9):1030-1039

Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.

Huntington's disease (HD) is a severe autosomal dominant neurodegenerative disorder characterized by a combination of motor, cognitive, and psychiatric symptoms, atrophy of the basal ganglia and the cerebral cortex, and inevitably progressive course resulting in death 5-20 years after manifestation of its symptoms. HD is caused by expansion of CAG repeats in the HTT gene, which leads to pathological elongation of the polyglutamine tract within the respective protein - huntingtin. In this review, we present a modern view on molecular biology of HD as a representative of the group of polyglutamine diseases, with an emphasis on conformational changes of mutant huntingtin, disturbances in its cellular processing, and proteolytic stress in degenerating neurons. Read More

Handb Clin Neurol 2018 ;157:761-775

Translational Neuroendocrine Research Unit, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.

Huntington disease (HD) is a paradigmatic autosomal-dominant adult-onset neurodegenerative disease. Since the identification of an abnormal expansion of a trinucleotide repeat tract in the huntingtin gene as the underlying genetic defect, a broad range of transgenic animal models of the disease has become available and these have helped to unravel the relevant molecular pathways in unprecedented detail. Of note, some of the most informative of these models develop thermoregulatory defects such as hypothermia, problems with adaptive thermogenesis, and an altered circadian temperature rhythm. Read More

Neurobiol Aging 2019 Feb 13;74:70-76. Epub 2018 Oct 13.

University of Exeter Medical School, University of Bristol, Exeter, UK. Electronic address:

Recent epigenome-wide association studies in Alzheimer's disease have highlighted consistent robust neuropathology-associated DNA hypermethylation of the ankyrin 1 (ANK1) gene in the cortex. The extent to which altered ANK1 DNA methylation is also associated with other neurodegenerative diseases is not currently known. In the present study, we used bisulfite pyrosequencing to quantify DNA methylation across 8 CpG sites within a 118 bp region of the ANK1 gene across multiple brain regions in Alzheimer's disease, Vascular dementia, Dementia with Lewy bodies, Huntington's disease, and Parkinson's disease. Read More

Mol Genet Genomic Med 2018 11 4;6(6):1140-1147. Epub 2018 Nov 4.

Berman Institute of Bioethics, Johns Hopkins University, Baltimore, Maryland.

Background: In 1983, Huntington's disease (HD) was the first genetic disease mapped using DNA polymorphisms. Shortly thereafter, presymptomatic genetic testing for HD began in the context of two research studies. One of these trials was at the Johns Hopkins University Huntington's Disease Center. Read More

Eur J Pharm Sci 2019 Jan 1;127:240-251. Epub 2018 Nov 1.

School of Pharmacy, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. Electronic address:

DB213 is an expanded CAG RNA inhibitor targeting polyglutamine diseases. This current study aims to investigate biopharmaceutic characteristics of DB213 as well as its brain uptake and distribution in C57 wild type mice, R6/2 Huntington's disease mice and Sprague-Dawley (SD) rats via intranasal administration. The biopharmaceutic characteristics of DB213 were investigated in vitro using Calu-3/MDCK/HEK293 cell lines and brain slices for its membrane transport, equilibrium dialysis for its plasma protein/brain tissue bindings and liver/brain microsomes incubation for its enzyme kinetics profiles. Read More

Acta Neuropathol Commun 2018 11 4;6(1):115. Epub 2018 Nov 4.

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, 72 E Concord Street, B7800, Boston, MA, 02118, USA.

The genetic basis of chronic traumatic encephalopathy (CTE) is poorly understood. Variation in transmembrane protein 106B (TMEM106B) has been associated with enhanced neuroinflammation during aging and with TDP-43-related neurodegenerative disease, and rs3173615, a missense coding SNP in TMEM106B, has been implicated as a functional variant in these processes. Neuroinflammation and TDP-43 pathology are prominent features in CTE. Read More

Behav Brain Res 2019 02 29;359:116-126. Epub 2018 Oct 29.

University of Tuebingen, Institute of Medical Genetics and Applied Genomics, Calwerstrasse 7, 72076 Tuebingen, Germany; University of Tuebingen, Centre for Rare Diseases, Calwerstrasse 7, 72076 Tuebingen, Germany. Electronic address:

Huntington disease is a hereditary neurodegenerative disease, in which patients display a broad range of clinical symptoms. Among these, impaired inhibitory control has been noted. The BACHD rat is a recently developed and established transgenic animal model for Huntington disease, and characterizing the presence of Huntington disease-like behavioural phenotypes in these animals is of importance. Read More

PLoS One 2018 26;13(10):e0206613. Epub 2018 Oct 26.

Molecular Imaging Center Antwerp (MICA), University of Antwerp, Wilrijk, Belgium.

The positron emission tomography (PET) tracer [18F]MNI-659, selective for phosphodiesterase 10A (PDE10A), is a promising tool to assess an early biomarker for Huntington's disease (HD). In this study we investigated [18F]MNI-659 uptake in the Q175 mouse model of HD. Given the focal striatal distribution of PDE10A as well as the striatal atrophy occurring in HD, the spatial normalization approach applied during the processing could sensibly affect the accuracy of the regional quantification. Read More

Comput Math Methods Med 2018 30;2018:9831252. Epub 2018 Sep 30.

Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei 230031, China.

A common feature that is typical of the patients with neurodegenerative (ND) disease is the impairment of motor function, which can interrupt the pathway from cerebrum to the muscle and thus cause movement disorders. For patients with amyotrophic lateral sclerosis disease (ALS), the impairment is caused by the loss of motor neurons. While for patients with Parkinson's disease (PD) and Huntington's disease (HD), it is related to the basal ganglia dysfunction. Read More

Mol Nutr Food Res 2018 12 8;62(23):e1800619. Epub 2018 Nov 8.

Renal, Vascular and Diabetes Research Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD), UAM, Madrid, Spain.

Scope: Huntington's disease (HD) is a rare progressive neurodegenerative disorder of genetic origin, with no definitive treatment. Unintentional weight loss (UWL) is a clinical feature of symptomatic HD subjects. To prevent UWL, a customized HD diet is designed and its impact on plasma miRNA HD footprint and neurological parameters is examined. Read More

Biomed Res Int 2018 24;2018:1012789. Epub 2018 Sep 24.

Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China.

Autophagy begins with the nucleation of phagophores, which then expand to give rise to the double-membrane autophagosomes. Autophagosomes ultimately fuse with lysosomes, where the cytosolic cargoes are degraded. Accumulation of autophagosomes is a hallmark of autophagy and neurodegenerative disorders including Alzheimer's and Huntington's disease. Read More

Neurodegener Dis 2018 18;18(5-6):239-253. Epub 2018 Oct 18.

Division of Human Genetics and UC Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Background: European studies identified the C9orf72 repeat expansion as the most frequent genetic alteration in patients with Huntington disease (HD)-like phenotypes but negative HD genetic testing.

Objective: To investigate C9orf72 repeat expansion frequency in individuals tested for HD in a North American tertiary referral laboratory.

Methods: Three hundred and seventy-three cases (115 positive and 258 negative for HD) were evaluated by genotyping PCR, with follow-up Southern blot and 5' repeat methylation status assessment by combined repeat-primed and methylation-specific PCR in a subset. Read More

PLoS One 2018 17;13(10):e0204735. Epub 2018 Oct 17.

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia.

Modeling of neurodegenerative diseases in vitro holds great promise for biomedical research. Human cell lines harboring a mutations in disease-causing genes are thought to recapitulate early stages of the development an inherited disease. Modern genome-editing tools allow researchers to create isogenic cell clones with an identical genetic background providing an adequate "healthy" control for biomedical and pharmacological experiments. Read More

Clin Nucl Med 2019 01;44(1):e1-e5

Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona.

Objective: Normalization to an appropriate reference region in F-FDG PET imaging may enhance diagnostic performance in Huntington disease (HD). We aimed to identify stable brain areas that could be used to model neurometabolic degeneration in HD correlating imaging (SUVrvalues at the basal ganglia [BBGG]) and clinical parameters (disease burden score [DBS]).

Materials And Methods: We performed brain F-FDG PET/CT in 38 manifest HD patients (meanage ± SD, 54 ± 14. Read More

Nat Commun 2018 10 15;9(1):4272. Epub 2018 Oct 15.

Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France.

Impaired hippocampal synaptic plasticity contributes to cognitive impairment in Huntington's disease (HD). However, the molecular basis of such synaptic plasticity defects is not fully understood. Combining live-cell nanoparticle tracking and super-resolution imaging, we show that AMPAR surface diffusion, a key player in synaptic plasticity, is disturbed in various rodent models of HD. Read More

RNA Biol 2018 26;15(10):1348-1363. Epub 2018 Oct 26.

b Crystallography and Molecular Biology Division , Saha Institute of Nuclear Physics, HBNI , Kolkata , India.

Altered expression levels of protein-coding genes and microRNAs have been implicated in the pathogenesis of Huntington's disease (HD). The involvement of other ncRNAs, especially long ncRNAs (lncRNA), is being realized recently and the related knowledge is still rudimentary. Using small RNA sequencing and PCR arrays we observed perturbations in the levels of 12 ncRNAs in HD mouse brain, eight of which had human homologs. Read More

Neurobiol Aging 2019 Jan 15;73:230.e9-230.e17. Epub 2018 Sep 15.

Departments of Neurology, Leiden University Medical Centre, Leiden, the Netherlands; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Genomewide association studies (GWASs) have contributed greatly to unraveling the genetic basis of Alzheimer's disease (AD). However, a large amount of "missing heritability" remains. In this exploratory study, we investigated the effect of cytosine-adenine-guanine (CAG) repeats in polyglutamine disease-associated genes (PDAGs) on the risk of AD and its expression. Read More

eNeuro 2018 Jul-Aug;5(4). Epub 2018 Oct 10.

Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University, Lund 22184, Sweden BMC D11.

The neurodegenerative Huntington's disease (HD) is caused by a polyglutamine (polyQ) amplification in the huntingtin protein (HTT). Currently there is no effective therapy available for HD; however, several efforts are directed to develop and optimize HTT-lowering methods to improve HD phenotypes. To validate these approaches, there is an immediate need for reliable, sensitive, and easily accessible methods to quantify HTT expression. Read More

Eur J Hum Genet 2019 01 5;27(1):20-21. Epub 2018 Oct 5.

Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Flemington Road, Parkville, 3052, Victoria, Australia.

J Mol Neurosci 2018 Nov 3;66(3):322-341. Epub 2018 Oct 3.

Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, 600 113, India.

In this study, we demonstrated for the first time the neuroprotective role of edaravone (Eda) (5 and 10 mg/kg b.w.), a potent free radical scavenger against the unilateral stereotaxic induction of quinolinic acid (QA) (300 nm/4 μl saline)-induced Huntington disease (HD)-like symptoms in behavioral, biochemical, and histological features in male Wistar rats striatum. Read More

Traffic Inj Prev 2018 1;19(7):708-714. Epub 2018 Oct 1.

a Department of Neurology , Leiden University Medical Center , Leiden , The Netherlands.

Objective: In clinical practice, patients with Huntington's disease (HD) often decide to solely drive in their own familiar neighborhoods and not on a motorway or in an unknown area. The aim of the study was to identify differences in driving performance between HD gene carriers and healthy individuals in simulated urban and motorway environments.

Methods: This cross-sectional study included 87 participants (28 premanifest HD, 30 manifest HD, 29 controls). Read More

Nat Commun 2018 09 28;9(1):3191. Epub 2018 Sep 28.

Center for Systems and Therapeutics & Taube/Koret Center for Neurodegenerative Disease, Gladstone Institutes, 1650 Owens St., San Francisco, CA, 94158, USA.

Huntington's disease is a progressive neurodegenerative disorder caused by polyglutamine-expanded mutant huntingtin (mHTT). Here, we show that the deubiquitinase Usp12 rescues mHTT-mediated neurodegeneration in Huntington's disease rodent and patient-derived human neurons, and in Drosophila. The neuroprotective role of Usp12 may be specific amongst related deubiquitinases, as the closely related homolog Usp46 does not suppress mHTT-mediated toxicity. Read More

PLoS One 2018 27;13(9):e0203837. Epub 2018 Sep 27.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Countless neurodegenerative diseases are associated with perverse multiple targets of cyclic nucleotide signalling, hastening neuronal death. Cilostazol, a phosphodiesterase-III inhibitor, exerts neuroprotective effects against sundry models of neurotoxicity, however, its role against Huntington's disease (HD) has not yet been tackled. Hence, its modulatory effect on several signalling pathways using the 3-nitropropionic acid (3-NP) model was conducted. Read More

NMR Biomed 2018 12 27;31(12):e4007. Epub 2018 Sep 27.

Singapore BioImaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore.

Recent studies suggest that neurodegenerative diseases could affect brain structure and function in disease-specific network patterns; however, how spontaneous activity affects structural covariance network (SC) is not clear. We hypothesized that hyper-excitability in Huntington disease (HD) disrupts the coordinated structural and functional connectivity, and treatment with memantine helps to reduce excitotoxicity and normalize the connectivity. MRI was conducted to measure somatosensory activation, resting-state functional-connectivity (rsFC), SC, amplitude of low frequency fluctuation (ALFF) and ALFF covariance (ALFFC) in the YAC128 mouse model of HD. Read More

Dement Geriatr Cogn Disord 2018 26;46(3-4):168-179. Epub 2018 Sep 26.

Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen,

Background: This study examines the efficacy of using quantitative measurements of motor dysfunction, compared to clinical ratings, in Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB).

Methods: In this cross-sectional study, 49 patients with a diagnosis of AD (n = 17), FTD (n = 19), or DLB (n = 13) were included and underwent cognitive testing, clinical motor evaluation, and quantitative motor tests: pronation/supination hand tapping, grasping and lifting, and finger and foot tapping.

Results: Our results revealed significantly higher Q-Motor values in pronation/supination and in grip lift force assessment in AD, FTD, and DLB compared to healthy controls (HC). Read More

Front Mol Neurosci 2018 4;11:318. Epub 2018 Sep 4.

Institute of Molecular Biosciences, University of Graz, Graz, Austria.

Huntington's disease (HD) is a neurodegenerative disorder that leads to progressive neuronal loss, provoking impaired motor control, cognitive decline, and dementia. So far, HD remains incurable, and available drugs are effective only for symptomatic management. HD is caused by a mutant form of the huntingtin protein, which harbors an elongated polyglutamine domain and is highly prone to aggregation. Read More

J Neuroinflammation 2018 Sep 18;15(1):269. Epub 2018 Sep 18.

Alzheimer's Disease Research Laboratory, Department of Neurology, Mass General Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, 114 16th Street, Charlestown, MA, 02129, USA.

Background: Misfolding of microtubule-associated protein tau (MAPT) within neurons into neurofibrillary tangles is an important pathological feature of Alzheimer's disease (AD). Tau pathology correlates with cognitive decline in AD and follows a stereotypical anatomical course; several recent studies indicate that tau pathology spreads inter-neuronally via misfolded tau "seeds." Previous research has focused on neurons as the source of these tau seeds. Read More

Mitochondrion 2018 Sep 13. Epub 2018 Sep 13.

Experimental Multiuser Laboratory (LEM), Graduate Program in Health Sciences (PPGCS), School of Medicine (PPGCS), Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná 80215-901, Brazil; Lico Kaesemodel Institute (ILK), Curitiba, Paraná 80240-000, Brazil. Electronic address:

Mitochondria are small cytosolic organelles and the main source of energy production for the cells, especially in the brain. This organelle has its own genome, the mitochondrial DNA (mtDNA), and genetic variants in this molecule can alter the normal energy metabolism in the brain, contributing to the development of a wide assortment of Neurological Disorders (ND), including neurodevelopmental syndromes, neurodegenerative diseases and neuropsychiatric disorders. These ND are comprised by a heterogeneous group of syndromes and diseases that encompass different cognitive phenotypes and behavioral disorders, such as autism, Asperger's syndrome, pervasive developmental disorder, attention deficit hyperactivity disorder, Huntington disease, Leigh Syndrome and bipolar disorder. Read More

J Biol Chem 2018 10 13;293(42):16127-16141. Epub 2018 Sep 13.

From the Center for NeuroGenetics,

Microsatellite expansions cause more than 40 neurological disorders, including Huntington's disease, myotonic dystrophy, and C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). These repeat expansion mutations can produce epeat-ssociated on-ATG (RAN) proteins in all three reading frames, which accumulate in disease-relevant tissues. There has been considerable interest in RAN protein products and their downstream consequences, particularly for the dipeptide proteins found in ALS/FTD. Read More

Neuropsychology 2018 Nov 13;32(8):958-965. Epub 2018 Sep 13.

Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University.

Objective: Unawareness of neuropsychiatric symptoms appears to be common in Huntington's disease (HD), but the clinical correlates of unawareness are unclear. Identifying predictors of unawareness is important for improving diagnosis of neuropsychiatric symptoms, and cognitive impairment, specifically executive impairment, may be a potential important predictor of unawareness. The authors examined whether unawareness of neuropsychiatric symptoms is more common in early HD compared to premanifest HD, and whether executive task performance was associated with awareness, independent of demographic, motor or mood variables. Read More

Eur J Hum Genet 2019 01 11;27(1):22-27. Epub 2018 Sep 11.

APHP, Genetic Department, Pitié-Salpêtrière University Hospital, Paris, France.

Predictive testing for Huntington disease (HD) in 25% at-risk individuals is testing with full knowledge, and sometimes assuming, that the parent does not want to know his status. The goal of this study was to understand: (1) the differences in the motivation between 25% and 50% at-risk individuals to be tested and (2) the consequences of "double disclosure", including parental reactions. Test requests from 25% at-risk individuals were rare (155/1611, 10%). Read More

Chin Med J (Engl) 2018 Sep;131(18):2216-2225

Department of Environmental Engineering, College of Environmental Science and Engineering, China West Normal University, Nanchong, Sichuan 637009, China.

Objective: A comprehensive review of the network regulation of exosomes and microRNAs (miRNAs) in neurodegenerative diseases was done, centering on the mechanism of the formation of exosomes and miRNAs and the sorting mechanism of exosomal miRNAs, with the aim to provide a theoretical basis in the search of biomarkers and the treatment of neurodegenerative diseases.

Data Sources: The comprehensive search used online literature databases including NCBI PubMed, Web of Science, Google Scholar, and Baidu Scholar.

Study Selection: The study selection was based on the following keywords: exosomes, miRNAs, central nervous system (CNS), and neurodegenerative diseases. Read More

Mol Cell 2018 09;71(5):675-688.e6

Neuroproteomics, Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany; Berlin Institute of Health (BIH), 10178 Berlin, Germany. Electronic address:

Self-propagating, amyloidogenic mutant huntingtin (mHTT) aggregates may drive progression of Huntington's disease (HD). Here, we report the development of a FRET-based mHTT aggregate seeding (FRASE) assay that enables the quantification of mHTT seeding activity (HSA) in complex biosamples from HD patients and disease models. Application of the FRASE assay revealed HSA in brain homogenates of presymptomatic HD transgenic and knockin mice and its progressive increase with phenotypic changes, suggesting that HSA quantitatively tracks disease progression. Read More

Neural Plast 2018 14;2018:4056383. Epub 2018 Aug 14.

Department of Morphological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a trinucleotide expansion in the gene, resulting in an extended polyglutamine tract in the protein huntingtin. HD is traditionally viewed as a movement disorder, but cognitive and neuropsychiatric symptoms also contribute to the clinical presentation. Depression is one of the most common psychiatric disturbances in HD, present even before manifestation of motor symptoms. Read More

Elife 2018 09 4;7. Epub 2018 Sep 4.

Institute of Pathophysiology, Focus Program Translational Neurosciences, University Medical Center, Mainz, Germany.

Catching primal functional changes in early, 'very far from disease onset' (VFDO) stages of Huntington's disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing two-photon Ca imaging, we revealed an early pattern of circuit dysregulation in the visual cortex - one of the first regions affected in premanifest Huntington's disease - characterized by an increase in activity, an enhanced synchronicity and hyperactive neurons. Read More