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Neurocase 2019 Feb 16:1-5. Epub 2019 Feb 16.

a Department of Neurology , Hospital Universitario 12 de Octubre , Madrid , Spain.

Semantic variant primary progressive aphasia (svPPA) is a clinical syndrome included in the frontotemporal dementia (FTD) spectrum. Unlike other forms of FTD, it is sporadic in the majority of cases and not commonly associated with motor neuron disease (MND). We describe a case of svPPA associated with MND in the same family, due to a mutation of the transactive response DNA binding protein (TARDBP) gene, and review the literature. Read More

J Neurochem 2019 Feb 4. Epub 2019 Feb 4.

Melbourne Dementia Research Centre at The Florey Institute of Neuroscience and Mental Health and The University of Melbourne, Parkville, Victoria, Australia.

Treatment with the dopamine (DA) precursor L-3,4-dihydroxyphenylalanine (L-DOPA) provides symptomatic relief arising from DA denervation in Parkinson's disease. Mounting evidence that DA autooxidation to neurotoxic quinones is involved in Parkinson's disease pathogenesis has raised concern about potentiation of oxidative stress by L-DOPA. The rate of DA quinone formation increases in the presence of excess redox-active iron (Fe), which is a pathological hallmark of Parkinson's disease. Read More

Acta Neurol Scand 2019 Feb 3. Epub 2019 Feb 3.

Department of Neurology, University of Piemonte Orientale, Maggiore della Carità Hospital, Novara, Italy.

Objectives: ALS is not only a motor disorder: more than 50% of patients have cognitive dysfunctions over the course of the disease. At the same time, mood disorders may also occur in ALS patients following diagnosis due to the fatal prognosis; however little data is available on any depression beforehand. Starting from these considerations, the aim of our study was to investigate the occurrence of depression in Italian ALS patients prior to diagnosis, evaluating its prevalence in the subjects who have developed cognitive dysfunctions and in those who did not. Read More

J Neurol 2019 Feb 1. Epub 2019 Feb 1.

Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.

This study systematically investigated the neuropsychological profile of language disturbance in frontotemporal dementia-motor neuron disease (FTD-MND) using a data-driven approach. Neuroanatomical correlates of language profiles were also examined. Patients with FTD-MND (N = 26), pure motor neuron disease (N = 34), progressive non-fluent aphasia (N = 30), semantic dementia (N = 17), and controls (N = 31) underwent comprehensive language assessments. Read More

Amyotroph Lateral Scler Frontotemporal Degener 2019 Jan 22:1-13. Epub 2019 Jan 22.

a Department of Neurology, Memory and Aging Center , University of California , San Francisco , CA , USA.

Objective: Behavioral variant frontotemporal dementia (bvFTD), is commonly considered the cognitive presentation of the frontotemporal dementia-motor neuron disease (FTD-MND) spectrum disorder. We evaluated the prevalence of primary progressive aphasia in a series of pathologically confirmed cases of FTD-MND spectrum.

Methods: Pathologically confirmed cases of frontotemporal lobar degeneration-motor neuron disease (FTLD-MND) were obtained from the UCSF brain bank. Read More

Neuropathology 2019 Jan 15. Epub 2019 Jan 15.

Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.

Globular glial tauopathies (GGTs) are four-repeat tauopathies characterized by the presence of two types of tau-positive globular glial inclusions (GGIs): globular oligodendrocytic and astrocytic inclusions (GOIs and GAIs). GGTs are classified into three different neuropathological subtypes: Types I, II and III. We report two patients with GGTs - a 76-year-old woman and a 70-year-old man - in whom the disease duration was 5 and 6 years, respectively. 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

Amyotroph Lateral Scler Frontotemporal Degener 2018 Dec 26:1-11. Epub 2018 Dec 26.

b Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London , London , UK.

Objectives: Cognitive and behavioral change in Amyotrophic Lateral Sclerosis (ALS) is well-accepted. Several screening tools have been developed to detect such changes. Further guidance on their use may come from a consideration of the rigor with which they were validated. Read More

Neuropathol Appl Neurobiol 2019 Feb;45(1):58-80

UK Dementia Research Institute, King's College London, London, Camberwell, UK.

Frontotemporal dementia (FTD) encompasses a collection of clinically and pathologically diverse neurological disorders. Clinical features of behavioural and language dysfunction are associated with neurodegeneration, predominantly of frontal and temporal cortices. Over the past decade, there have been significant advances in the understanding of the genetic aetiology and neuropathology of FTD which have led to the creation of various disease models to investigate the molecular pathways that contribute to disease pathogenesis. Read More

Int J Mol Sci 2018 Dec 20;20(1). Epub 2018 Dec 20.

Department of Neurology ComplejoHospitalario de Navarra (CHN), IdiSNA (Navarra Institute for Health Research), Irunlarrea 3, 31008 Pamplona, Spain.

(1) Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with an overlap in clinical presentation and neuropathology. Common and differential mechanisms leading to protein expression changes and neurodegeneration in ALS and FTD were studied trough a deep neuroproteome mapping of the spinal cord. (2) Methods: A liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the spinal cord from ALS-TAR DNA-binding protein 43 () subjects, ubiquitin-positive frontotemporal lobar degeneration (FTLD-U) subjects and controls without neurodegenerative disease was performed. Read More

Front Neurol 2018 5;9:1063. Epub 2018 Dec 5.

Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States.

Now that genetic testing can identify persons at risk for developing amyotrophic lateral sclerosis (ALS) many decades before symptoms begin, there is a critical need for biomarkers that signal the onset and progression of degeneration. The search for candidate disease biomarkers in patients with mutations in the gene has included imaging, physiology, and biofluid measurements. In cross-sectional imaging studies, C9+ ALS patients display diffuse reductions of gray and white matter integrity compared to ALS patients without mutations. Read More

JAMA Neurol 2018 Dec 3. Epub 2018 Dec 3.

Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.

Importance: Neuronal and axonal destruction are hallmarks of neurodegenerative diseases, but it is difficult to estimate the extent and progress of the damage in the disease process.

Objective: To investigate cerebrospinal fluid (CSF) levels of neurofilament light (NFL) protein, a marker of neuroaxonal degeneration, in control participants and patients with dementia, motor neuron disease, and parkinsonian disorders (determined by clinical criteria and autopsy), and determine its association with longitudinal cognitive decline.

Design, Setting, And Participants: In this case-control study, we investigated NFL levels in CSF obtained from controls and patients with several neurodegenerative diseases. Read More

Acta Neuropathol 2019 Jan 3;137(1):27-46. Epub 2018 Dec 3.

Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

TAR DNA-binding protein 43 (TDP-43) aggregation is the most common pathological hallmark in frontotemporal dementia (FTD) and characterizes nearly all patients with motor neuron disease (MND). The earliest stages of TDP-43 pathobiology are not well-characterized, and whether neurodegeneration results from TDP-43 loss-of-function or aggregation remains unclear. In the behavioral variant of FTD (bvFTD), patients undergo selective dropout of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices. Read More

PLoS One 2018 29;13(11):e0208255. Epub 2018 Nov 29.

Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.

Background: The spectrum of motor neuron disease (MND) includes numerous phenotypes with various life expectancies. The degree of upper and lower motor neuron involvement can impact prognosis. Phase sensitive inversion recovery (PSIR) imaging has been shown to detect in vivo gray matter (GM) and white matter (WM) atrophy in the spinal cord of other patient populations but has not been explored in MND. Read More

Handb Clin Neurol 2018 ;159:195-203

Brain and Mind Centre, University of Sydney Medical School, Sydney, NSW, Australia.

Frontotemporal dementia (FTD) and related diseases are important causes of younger-onset dementia. Falls may be a source of morbidity and mortality in FTD, but remain underreported, and very few high-quality studies have been performed. In this chapter, we briefly review the clinical features of FTD and related syndromes such as motor neuron disease (MND) and atypical parkinsonian syndromes, such as progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Read More

J Neurol Neurosurg Psychiatry 2018 Nov 22. Epub 2018 Nov 22.

Department of Neuroinflammation, UCL Institute of Neurology, London, UK.

Adult-onset leukodystrophies and genetic leukoencephalopathies comprise a diverse group of neurodegenerative disorders of white matter with a wide age of onset and phenotypic spectrum. Patients with white matter abnormalities detected on MRI often present a diagnostic challenge to both general and specialist neurologists. Patients typically present with a progressive syndrome including various combinations of cognitive impairment, movement disorders, ataxia and upper motor neuron signs. Read More

Handb Clin Neurol 2018 ;157:749-760

Department of Neurodegenerative Diseases and Gerontopsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany.

Amyotrophic lateral sclerosis (ALS) is the major adult-onset motor neuron disease, and is clinically, pathologically, and genetically associated with frontotemporal dementia, the second cause of dementia in the elderly. Here, we review the evidence linking thermoregulation and ALS. Indeed, while ALS is not classically associated with defective thermoregulatory function, its progression severely affects key brain regions controlling body temperature and impacts multiple sensors and effectors of this homeostatic function. Read More

Acta Neuropathol Commun 2018 Nov 19;6(1):125. Epub 2018 Nov 19.

Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, UK.

A hexanucleotide repeat expansion (HRE) within the chromosome 9 open reading frame 72 (C9orf72) gene is the most prevalent cause of amyotrophic lateral sclerosis/fronto-temporal dementia (ALS/FTD). Current evidence suggests HREs induce neurodegeneration through accumulation of RNA foci and/or dipeptide repeat proteins (DPR). C9orf72 patients are known to have transactive response DNA binding protein 43 kDa (TDP-43) proteinopathy, but whether there is further cross over between C9orf72 pathology and the pathology of other ALS sub-types has yet to be revealed. Read More

Acta Neuropathol 2019 Jan 19;137(1):47-69. Epub 2018 Nov 19.

Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Insoluble aggregates containing TDP-43 are widely observed in the diseased brain, and defined as "TDP-43 pathology" in a spectrum of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease and ALS with frontotemporal dementia. Here we report that Betz cells of patients with TDP-43 pathology display a distinct set of intracellular defects especially at the site of nuclear membrane, mitochondria and endoplasmic reticulum (ER). Numerous TDP-43 mouse models have been generated to discern the cellular and molecular basis of the disease, but mechanisms of neuronal vulnerability remain unknown. Read More

Proc Natl Acad Sci U S A 2018 12 15;115(49):E11485-E11494. Epub 2018 Nov 15.

Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205;

The ubiquitin-like protein ubiquilin 2 (UBQLN2) has been genetically and pathologically linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but its normal cellular functions are not well understood. In a search for UBQLN2-interacting proteins, we found an enrichment of stress granule (SG) components, including ALS/FTD-linked heterogeneous ribonucleoprotein fused in sarcoma (FUS). Through the use of an optimized SG detection method, we observed UBQLN2 and its interactors at SGs. Read More

NeuroRehabilitation 2018 ;43(4):443-471

PenCLAHRC, University of Exeter Medical School, Exeter, UK.

Background: Despite its potentially significant impact, cognitive disability may be overlooked in a number of progressive neurodegenerative conditions, as other difficulties dominate the clinical picture.

Objective: We examined the extent, nature and range of the research evidence relating to cognitive rehabilitation, self-management, psychotherapeutic and caregiver support interventions in Parkinsonian disorders, multiple sclerosis (MS), frontotemporal dementias (FTD), motor neuron disease and Huntington's disease.

Methods: Scoping review based on searches of MEDLINE and CINAHL up to 15 March 2016. Read More

Transl Res 2019 Feb 12;204:19-30. Epub 2018 Oct 12.

Department of Chemistry, Brooklyn College, Brooklyn, NewYork; Ph.D. Programs in Chemistry, Biochemistry, and Biology, The Graduate Center of the City University of New York, New York, New York. Electronic address:

Amyotrophic lateral sclerosis (ALS) is the third most common adult onset neurodegenerative disorder worldwide. It is generally characterized by progressive paralysis starting at the limbs ultimately leading to death caused by respiratory failure. There is no cure and current treatments fail to slow the progression of the disease. Read More

Hum Mol Genet 2018 12;27(23):4103-4116

Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven-University of Leuven, Leuven, Belgium.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases characterized by the progressive loss of specific groups of neurons. Due to clinical, genetic and pathological overlap, both diseases are considered as the extremes of one disease spectrum and in a number of ALS and FTD patients, fused in sarcoma (FUS) aggregates are present. Even in families with a monogenetic disease cause, a striking variability is observed in disease presentation. Read More

Front Neurosci 2018 15;12:669. Epub 2018 Oct 15.

School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.

Age is the common risk factor for both neurodegenerative and neuromuscular diseases. Alzheimer disease (AD), a neurodegenerative disorder, causes dementia with age progression while GNE myopathy (GNEM), a neuromuscular disorder, causes muscle degeneration and loss of muscle motor movement with age. Individuals with mutations in presenilin or amyloid precursor protein (APP) gene develop AD while mutations in GNE (UDP -acetylglucosamine 2 epimerase/-acetyl Mannosamine kinase), key sialic acid biosynthesis enzyme, cause GNEM. Read More

Proc Natl Acad Sci U S A 2018 11 29;115(46):E10941-E10950. Epub 2018 Oct 29.

Department of Physiology, National University of Singapore, Republic of Singapore 117549;

TDP-43 aggregates in neurons and glia are the defining pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), raising the possibility of glial damage in the disease pathogenesis. However, the normal physiological functions of TDP-43 in glia are largely unknown. To address how TDP-43 may be required for oligodendroglial functions we selectively deleted TDP-43 in mature oligodendrocytes in mice. Read More

Amyotroph Lateral Scler Frontotemporal Degener 2018 Oct 29:1-7. Epub 2018 Oct 29.

a Brain & Mind Centre , University of Sydney , Camperdown , NSW , Australia , and.

Objectives: Apathy is the most common behavioral symptom of amyotrophic lateral sclerosis (ALS). Despite its known impact on caregiver wellbeing, apathy is typically considered a unitary construct making assessment and targeting treatment problematic. The aim of this study was to explore the relationship between caregiver burden and the behavioral, cognitive, and emotional symptoms of apathy in ALS. Read More

Genes Dev 2018 11 26;32(21-22):1380-1397. Epub 2018 Oct 26.

Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.

Cells undergo metabolic adaptation during environmental changes by using evolutionarily conserved stress response programs. This metabolic homeostasis is exquisitely regulated, and its imbalance could underlie human pathological conditions. We report here that C9orf72, which is linked to the most common forms of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), is a key regulator of lipid metabolism under stress. 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

Anat Sci Int 2019 Jan 25;94(1):11-22. Epub 2018 Oct 25.

Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, 602-8566, Japan.

α-Synuclein, the major component of Lewy bodies (LBs) and Lewy neurites (LNs), is expressed in presynapses under physiologically normal conditions and is involved in synaptic function. Abnormal intracellular aggregates of misfolded α-synuclein such as LBs and LNs are pathological hallmarks of synucleinopathies, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). According to previous studies using pathological models overexpressing α-synuclein, high expression of this protein in neurons is a critical risk factor for neurodegeneration. Read More

Nucleic Acids Res 2019 Jan;47(1):341-361

Neuronal Translational Control Research Group, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Hamburg 20251, Germany.

The RNA-binding protein TDP-43 is heavily implicated in neurodegenerative disease. Numerous patient mutations in TARDBP, the gene encoding TDP-43, combined with data from animal and cell-based models, imply that altered RNA regulation by TDP-43 causes Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. However, underlying mechanisms remain unresolved. Read More

Neuron 2018 Nov 18;100(4):816-830.e7. Epub 2018 Oct 18.

Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address:

Through the generation of humanized FUS mice expressing full-length human FUS, we identify that when expressed at near endogenous murine FUS levels, both wild-type and ALS-causing and frontotemporal dementia (FTD)-causing mutations complement the essential function(s) of murine FUS. Replacement of murine FUS with mutant, but not wild-type, human FUS causes stress-mediated induction of chaperones, decreased expression of ion channels and transporters essential for synaptic function, and reduced synaptic activity without loss of nuclear FUS or its cytoplasmic aggregation. Most strikingly, accumulation of mutant human FUS is shown to activate an integrated stress response and to inhibit local, intra-axonal protein synthesis in hippocampal neurons and sciatic nerves. Read More

Proc Natl Acad Sci U S A 2018 10 17;115(44):E10495-E10504. Epub 2018 Oct 17.

Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200;

UBQLN2 is one of a family of proteins implicated in ubiquitin-dependent protein quality control and integrally tied to human neurodegenerative disease. Whereas wild-type UBQLN2 accumulates in intraneuronal deposits in several common age-related neurodegenerative diseases, mutations in the gene encoding this protein result in X-linked amyotrophic lateral sclerosis/frontotemporal dementia associated with TDP43 accumulation. Using in vitro protein analysis, longitudinal fluorescence imaging and cellular, neuronal, and transgenic mouse models, we establish that UBQLN2 is intrinsically prone to self-assemble into higher-order complexes, including liquid-like droplets and amyloid aggregates. Read More

Mol Neurodegener 2018 10 16;13(1):55. Epub 2018 Oct 16.

Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Leuven - University of Leuven, Leuven, Belgium.

Background: TAR DNA binding protein 43 (TDP-43) is the main disease protein in most patients with amyotrophic lateral sclerosis (ALS) and about 50% of patients with frontotemporal dementia (FTD). TDP-43 pathology is not restricted to patients with missense mutations in TARDBP, the gene encoding TDP-43, but also occurs in ALS/FTD patients without known genetic cause or in patients with various other ALS/FTD gene mutations. Mutations in progranulin (GRN), which result in a reduction of ~ 50% of progranulin protein (PGRN) levels, cause FTD with TDP-43 pathology. Read More

Int J Mol Sci 2018 Oct 12;19(10). Epub 2018 Oct 12.

Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.

Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressing neurodegenerative disease affecting motor neurons, and frontotemporal dementia (FTD) is a behavioural disorder resulting in early-onset dementia. Hexanucleotide (G4C2) repeat expansions in the gene encoding chromosome 9 open reading frame 72 () are the major cause of familial forms of both ALS (~40%) and FTD (~20%) worldwide. The C9orf72 repeat expansion is known to form abnormal nuclei acid structures, such as hairpins, G-quadruplexes, and R-loops, which are increasingly associated with human diseases involving microsatellite repeats. Read More

Neuron 2018 Oct;100(1):75-90.e5

Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address:

α-Synuclein (αS) regulates vesicle exocytosis but forms insoluble deposits in Parkinson's disease (PD). Developing disease-modifying therapies requires animal models that reproduce cardinal features of PD. We recently described a previously unrecognized physiological form of αS, α-helical tetramers, and showed that familial PD-causing missense mutations shift tetramers to aggregation-prone monomers. Read More

J Neurol Neurosurg Psychiatry 2019 Feb 8;90(2):122-123. Epub 2018 Oct 8.

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK

Amyotroph Lateral Scler Frontotemporal Degener 2018 Sep 28:1-6. Epub 2018 Sep 28.

a Department of Neurology , Nordland Hospital , Bodø , Norway.

Objective: There are some indications of increasing incidence of amyotrophic lateral sclerosis (ALS). Awareness of cognitive impairment in ALS has increased in recent years. We describe the epidemiology and clinical features of ALS in a county in northern Norway over a period of 15 years. Read More

J Neurol Neurosurg Psychiatry 2018 Sep 26. Epub 2018 Sep 26.

Department of Neurology, University of Ulm, Ulm, Germany.

Objective: To determine the evolution and profile of cognitive and behavioural deficits in amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) to disentangle the development of FTD in ALS and vice versa.

Methods: In a prospective design, cognitive and behavioural profiles of 762 patients with motor predominant ALS (flail arm/leg syndrome, primary lateral sclerosis, pseudobulbar palsy, ALS) and behavioural predominant FTD (bvFTD, ALS-FTD) were determined and caregivers of patients with ALS were asked on the evolution of behavioural symptoms. Data were compared with 49 healthy controls. Read More

Brain 2018 Oct;141(10):2878-2894

Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK.

Deafferentation of motor neurons as a result of defective sensory-motor connectivity is a critical early event in the pathogenesis of spinal muscular atrophy, but the underlying molecular pathways remain unknown. We show that restoration of ubiquitin-like modifier-activating enzyme 1 (UBA1) was sufficient to correct sensory-motor connectivity in the spinal cord of mice with spinal muscular atrophy. Aminoacyl-tRNA synthetases, including GARS, were identified as downstream targets of UBA1. Read More

Front Psychol 2018 3;9:1615. Epub 2018 Sep 3.

School of Psychology, The University of Sydney, Sydney, NSW, Australia.

The genetic mutation is the most common cause of familial frontotemporal dementia (FTD) and motor neuron disease (MND). Previous family studies suggest that while some common clinical features may distinguish gene carriers from sporadic patients, the clinical features, age of onset and disease progression vary considerably in affected patients. Whilst disease presentations may vary across families, age at disease onset appears to be relatively uniform within each family. Read More

J Neurol Neurosurg Psychiatry 2019 Jan 17;90(1). Epub 2018 Sep 17.

Western Clinical School, University of Sydney, Sydney, NSW 2145, Australia

Med Genet 2018 13;30(2):252-258. Epub 2018 Jul 13.

1Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease, affecting the upper and/or lower motor neurons. However, extramotor symptoms can also occur; cognitive deficits are present in more than 40% of patients and 5-8% of ALS patients develop frontotemporal dementia. There is no effective treatment for ALS and median survival is 2-3 years after onset. Read More

Neuropathology 2018 Dec 14;38(6):583-590. Epub 2018 Sep 14.

Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Dynactin forms a protein complex with dynein that retrogradely transports cargo along microtubules. Dysfunction of this dynein-dynactin complex causes several neurodegenerative diseases such as Perry syndrome, motor neuron diseases and progressive supranuclear palsy. Recently, we reported colocalization of phosphorylated α-synuclein (p-SNCA) and the largest subunit of dynactin (DCTN1) in Lewy body (LB)-like structures in Perry syndrome. Read More

Acta Neurol Scand 2019 Feb 24;139(2):118-127. Epub 2018 Sep 24.

Neuromuscular Research Unit, Instituto de Investigación Sanitaria la Fe (IIS La Fe), Valencia, Spain.

Objectives: An enlarged width of the third ventricle (WTV) has been described in amyotrophic lateral sclerosis (ALS) patients, although its clinical meaning is unknown. The aims of this study were to evaluate the contribution of demographical, clinical and genetic factors to the WTV in different motor neuron disease (MND) phenotypes and to assess its brain structural correlates.

Materials And Methods: The WTV was measured by transcranial ultrasound in 107 MND patients (82 diagnosed with classical ALS, 16 with progressive muscular atrophy and 9 with primary lateral sclerosis) and 25 controls. Read More

Int Rev Neurobiol 2018 2;139:443-462. Epub 2018 Aug 2.

1st Neurology Department, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

Placebo is an intervention with no therapeutic effect that is used as a control in randomized controlled trials (RCTs). Placebo effects and responses can produce a beneficial effect that cannot be attributed to the properties of the intervention itself, since it is usually inactive, and should, therefore, be due to the patient's expectations about treatment (placebo effects), or confounding factors such as natural history, co-interventions, biases, among other co-factors (placebo responses). However, adverse events (AEs) may occur when using a placebo intervention, a phenomenon that is called nocebo. Read More

J Mol Neurosci 2018 Oct 23;66(2):172-179. Epub 2018 Aug 23.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, P. O. Box: 1417755469, Tehran, Iran.

Extracellular vesicles (EVs) are membrane-bound vesicles, including exosomes and microvesicles. EVs are nanometer sized, found in physiological fluids such as urine, blood, cerebro-spinal fluid (CSF), with a capacity of transferring various biological materials such as microRNAs, proteins, and lipids among cells without direct cell-to-cell contact. Many cells in the nervous system have been shown to release EVs. Read More

Psychogeriatrics 2018 Jul;18(4):307-312

National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.

Background: The behavioural variant of frontotemporal dementia (bvFTD) is the most common phenotype of frontotemporal lobar degeneration (FTLD). FTLD is divided into three main pathological subtypes: tau-positive FTLD (FTLD-tau), FTLD-TAR DNA-binding protein (TDP), and FTLD-Fused in sarcoma (FUS). At present, it is difficult to predict the underlying pathological subtypes of sporadic bvFTD before a patient's death. Read More

Elife 2018 08 21;7. Epub 2018 Aug 21.

Department of Neuroscience, Mayo Clinic, Jacksonville, United States.

New analyses shift the view that some forms of amyotrophic lateral sclerosis and frontotemporal dementia are due to defects in a single RNA-binding protein. Read More

Nat Med 2018 Oct 20;24(10):1579-1589. Epub 2018 Aug 20.

Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

Amyotrophic lateral sclerosis (ALS) is a heterogeneous motor neuron disease for which no effective treatment is available, despite decades of research into SOD1-mutant familial ALS (FALS). The majority of ALS patients have no familial history, making the modeling of sporadic ALS (SALS) essential to the development of ALS therapeutics. However, as mutations underlying ALS pathogenesis have not yet been identified, it remains difficult to establish useful models of SALS. Read More

PLoS One 2018 17;13(8):e0200626. Epub 2018 Aug 17.

Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, Massachusetts.

Huntington's Disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by deleterious expansion of CAG repeats in the Huntingtin gene and production of neurotoxic mutant Huntingtin protein (mHTT). The key pathological feature of HD is a profound degeneration of the striatum and a loss of cortical volume. The initial loss of indirect pathway (D2) medium spiny neuron (MSN) projections in early stages of HD, followed by a loss of direct pathway (D1) projections in advanced stages has important implications for the trajectory of motor and cognitive dysfunction in HD, but is not yet understood. Read More