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Cortex 2019 Mar 19;117:257-265. Epub 2019 Mar 19.

Neurodegenerative Disease Unit, Department of Clinical Research in Neurology, University of Bari "Aldo Moro", Lecce, Italy; Neurodegenerative Disease Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, Italy. Electronic address:

In amyotrophic lateral sclerosis (ALS), memory deficits may be primary or secondary to executive dysfunction. We assessed episodic memory and executive function of nondemented ALS patients, comparing episodic memory profiles and learning rates of ALS patients with those of mild cognitive impairment (MCI) subjects and cognitively healthy controls (HC). In a multidisciplinary tertiary centre for motor neuron disease, 72 nondemented ALS patients, 57 amnestic MCI (aMCI), 89 single non amnestic MCI with compromised executive functions (dysexecutive MCI), and 190 HC were enrolled. Read More

Neurobiol Aging 2019 Mar 27. Epub 2019 Mar 27.

Division for Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Theme Aging, Unit for Hereditary Dementias QA12, Stockholm, Sweden. Electronic address:

Frontotemporal dementia (FTD) is the second most common early-onset dementia. Up to half of the cases are familial, and several mutations have been identified as pathogenic. Repeat expansion mutations in C9orf72 are the most common genetic cause of FTD and are particularly frequent in Sweden and Finland. Read More

J Neurol Neurosurg Psychiatry 2019 Apr 9. Epub 2019 Apr 9.

Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry, The Sahlgrenska AcademyUniversity of Gothenburg, Mölndal, Sweden.

In the management of neurological diseases, the identification and quantification of axonal damage could allow for the improvement of diagnostic accuracy and prognostic assessment. Neurofilament light chain (NfL) is a neuronal cytoplasmic protein highly expressed in large calibre myelinated axons. Its levels increase in cerebrospinal fluid (CSF) and blood proportionally to the degree of axonal damage in a variety of neurological disorders, including inflammatory, neurodegenerative, traumatic and cerebrovascular diseases. Read More

Front Neurol 2019 19;10:234. Epub 2019 Mar 19.

Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States.

Single time point positron emission tomography (PET) studies of patients with amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD), have demonstrated hypometabolism or hypermetabolism in certain brain regions. To determine whether longitudinal (at baseline and 20.4 months later) PET and magnetic resonance imaging (MRI) reveal evolving brain imaging pathology corresponding to clinical progression in a patient with ALS-FTD, cerebral glucose metabolic rate, cortical thickness (CT) and cortical area (CA) were obtained and symmetric percent change (SPC) for each calculated. Read More

Yakugaku Zasshi 2019 ;139(4):609-615

Laboratory of Biochemistry, School of Pharmacy, Nihon University.

Diseases of the motor-conducting system that cause moving disability affect socio-economic activity as well as human dignity. Neurolathyrism, konzo, and amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC) have attracted researchers to study the pathology of motor neuron (MN) diseases such as ALS. I have been studying neurolathyrism, which is caused by overconsumption of a legume grass pea (Lathyrys sativus L. Read More

Front Neurosci 2019 11;13:175. Epub 2019 Mar 11.

Department of Neuroscience, Azienda Ospedaliera Universitaria Modena, St. Agostino- Estense Hospital, Modena, Italy.

The historical view that Amyotrophic Lateral Sclerosis (ALS) as a pure motor disorder has been increasingly challenged by the discovery of cognitive and behavioral changes in the spectrum of Frontotemporal Dementia (FTD). Less recognized and still significant comorbidities that ALS patients may present are prior or concomitant psychiatric illness, such as psychosis and schizophrenia, or mood disorders. These non-motor symptoms disturbances have a close time relationship with disease onset, may constitute part of a larger framework of network disruption in motor neuron disorders, and may impact ALS patients and families, with regards to ethical choices and end-of-life decisions. Read More

Neurodegener Dis 2018 20;18(5-6):310-314. Epub 2019 Mar 20.

Deptartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy.

The aim of our study was to evaluate the role of mutations in the MAPT gene in patients with pure amyotrophic lateral sclerosis (ALS). A cohort of 120 ALS patients, both sporadic and familial, without cognitive impairment was analyzed by next-generation sequencing with a multiple-gene panel comprising 23 genes, including MAPT, known to be associated with ALS and frontotemporal dementia. The presence of the C9orf72 expansion was also investigated. Read More

Amyotroph Lateral Scler Frontotemporal Degener 2019 Mar 20:1-4. Epub 2019 Mar 20.

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

Objective: To describe a patient with facial onset sensory and motor neuronopathy (FOSMN) carrying heterozygous mutations in both TARDBP and SQSTM1 genes.

Methods: The patient underwent neurological, neuropsychological, and neurophysiological examinations. Brain magnetic resonance imaging (MRI) and extensive genetic analysis were also performed. Read More

Hell J Nucl Med 2019 Jan-Apr;22 Suppl:133-146

1st Otolaryngology Dept, Medical School, Aristotle University of Thessaloniki, Aristotle University Campus, 54124, Thessaloniki, Greece.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease that belongs to the group of motor neuron diseases. Motor deficits like reduce in tongue strength, may coexist with cognitive deficits compatible with frontotemporal dementia (FTD), also known as frontotemporal lobar degeneration (FTLD). FTD is a neurodegenerative syndrome with two main clinical variants: behavioral (bvFTD) and language or Primary Progressive Aphasia (PPA). Read More

Acta Neuropathol 2019 Mar 14. Epub 2019 Mar 14.

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY, 10065, USA.

Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10), a mitochondrial protein of unknown function, cause a disease spectrum with clinical features of motor neuron disease, dementia, myopathy and cardiomyopathy. To investigate the pathogenic mechanisms of CHCHD10, we generated mutant knock-in mice harboring the mouse-equivalent of a disease-associated human S59L mutation, S55L in the endogenous mouse gene. CHCHD10 mice develop progressive motor deficits, myopathy, cardiomyopathy and accelerated mortality. Read More

Acta Neuropathol 2019 Mar 14. Epub 2019 Mar 14.

Inserm U1081, CNRS UMR7284, IRCAN, CHU de Nice, Medicine School, Université Côte d'Azur, 28 av de Valombrose, 06107, Nice Cedex 2, France.

Recently, we provided genetic basis showing that mitochondrial dysfunction can trigger motor neuron degeneration, through identification of CHCHD10 encoding a mitochondrial protein. We reported patients, carrying the p.Ser59Leu heterozygous mutation in CHCHD10, from a large family with a mitochondrial myopathy associated with motor neuron disease (MND). Read More

Neuropathology 2019 Apr 7;39(2):135-140. Epub 2019 Mar 7.

Clinical Neuropathology, King's College Hospital, NHS Foundation Trust, London, UK.

Sporadic prion diseases are fatal neurodegenerative disorders characterized clinically by rapidly progressive dementia and myoclonus. Variably protease-sensitive prionopathy (VPSPr) is a recently identified sporadic human prion disorder that may present with a lengthy atypical clinical history. Here, we describe a case of VPSPr in a patient with a long history of suspected frontotemporal dementia (FTD). Read More

J Neurol 2019 May 7;266(5):1211-1221. Epub 2019 Mar 7.

Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, showa-ku, Nagoya, Aichi, 466-8550, Japan.

Background: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, hereditary neuromuscular disease characterized by muscle atrophy, weakness, contraction fasciculation, and bulbar involvement. Although the causative gene, androgen receptor, has been identified, the development of novel therapeutics for SBMA is incomplete. In this study, the efficacy and safety of leuprorelin acetate administration for patients with SBMA, using the pooled data of two randomized-controlled trials, was studied. Read More

J Neurol 2019 May 5;266(5):1079-1090. Epub 2019 Mar 5.

Department of Neurology, Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, CIBERNED, Santander, Spain.

Objective: To report a kindred with an association between hereditary primary lateral sclerosis (PLS) and progressive nonfluent aphasia.

Patients And Methods: Six members from a kindred with 15 affected individuals spanning three generations, suffered from spasticity without muscle atrophy or fasciculation, starting in the lower limbs and spreading to the upper limbs and bulbar musculature, followed by effortful speech, nonfluent language and dementia, in 5 deceased members. Disease onset was during the sixth decade of life, or later. Read More

J Neurol 2019 Mar 5. Epub 2019 Mar 5.

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

The objective of the study is to determine the utility of a simple reaction time task as a marker of general cognitive decline across the frontotemporal lobar degeneration (FTLD) spectrum and in Alzheimer's disease (AD). One hundred and twelve patients presenting with AD or FTLD affecting behaviour (behavioural-variant frontotemporal dementia), language (progressive non fluent aphasia, logopenic progressive aphasia, semantic dementia) or motor function (corticobasal syndrome, progressive supranuclear palsy, frontotemporal dementia-motor neuron disease) and 25 age-matched healthy controls completed the Psychomotor Vigilance Task (PVT), a 3-min reaction time (RT) task. The proportion of lapses (RT > 500 ms) was significantly increased in dementia patients compared to healthy controls, except for semantic dementia, and correlated with all cognitive functions except language. Read More

Int J Radiat Biol 2019 Mar 4:1-9. Epub 2019 Mar 4.

a National Council on Radiation Protection and Measurements , Bethesda , MD , USA.

Understanding the health consequences of exposure to radiation received gradually over time is critically needed. The National Aeronautics and Space Administration (NASA) bases its safety standards on the acute exposures received by Japanese atomic bomb survivors. Such a brief exposure differs appreciably from the chronic radiation received during a two to three year mission to Mars. Read More

Neurocase 2018 Oct - Dec;24(5-6):301-305. 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 May 28;139(5):438-445. Epub 2019 Feb 28.

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

Objectives: Amyotrophic lateral sclerosis (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 are 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 Apr 1;266(4):921-933. 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 Apr 15;39(2):111-119. 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

Neuroscience 2019 01;396:A3-A20

Department of Neuroscience, Brown University, Providence, Rhode Island 02912, United States; Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, Rhode Island 02912, United States. Electronic address:

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that has significant overlap with frontotemporal dementia (FTD). Mutations in specific genes have been identified that can cause and/or predispose patients to ALS. However, the clinical variability seen in ALS patients suggests that additional genes impact pathology, susceptibility, severity, and/or progression of the disease. 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

Neurol Sci 2019 Mar 15;40(3):515-521. Epub 2018 Dec 15.

Vita-Salute San Raffaele University, Milan, Italy.

Objective: The hexanucleotide repeat expansion in C9orf72 is an associated genetic cause in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In the "ALS/FTD" spectrum prevails clinical heterogeneity and an in vivo knowledge of the underling brain dysfunction in patients carrying C9orf72 mutation remain limited and only described at group level. The study aimed to assess the brain metabolic alterations characterizing patients with C9orf72 mutation using FDG-PET in single individuals. 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

Mol Neurodegener 2018 12 4;13(1):63. Epub 2018 Dec 4.

Department of Neurology, The McGovern Medical School of UT Health, Houston, TX, USA.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two fatal neurodegenerative disorders with considerable clinical, pathological and genetic overlap. Both disorders are characterized by the accumulation of pathological protein aggregates that contain a number of proteins, most notably TAR DNA binding protein 43 kDa (TDP-43). Surprisingly, recent clinical studies suggest that dyslipidemia, high body mass index, and type 2 diabetes mellitus are associated with better clinical outcomes in ALS. 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 2019 May 22;90(5):543-554. 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 11 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 02 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