11,169 results match your criteria Frontotemporal Lobe Dementia


Network localization of heterogeneous neuroimaging findings.

Brain 2018 Dec 14. Epub 2018 Dec 14.

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical Center, Boston, MA, USA.

Studies of the same disease often implicate different brain regions, contributing to a perceived reproducibility crisis in neuroimaging. Here, we leverage the normative human brain connectome to test whether seemingly heterogeneous neuroimaging findings localize to connected brain networks. We use neurodegenerative disease, and specifically Alzheimer's disease, as our example as it is one of the diseases that has been studied the most using neuroimaging. Read More

View Article
December 2018

Phenotypic variability and neuropsychological findings associated with C9orf72 repeat expansions in a Bulgarian dementia cohort.

PLoS One 2018 14;13(12):e0208383. Epub 2018 Dec 14.

Karolinska Institutet, Dept NVS, Division for Neurogeriatrics, Bioclinicum, Akademiska stråket, Solna, Sweden.

Background: The GGGGCC repeat expansion in the C9orf72 gene was recently identified as a major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in several European populations. The objective of this study was to determine the frequency of C9orf72 repeat expansions in a Bulgarian dementia cohort and to delineate the associated clinical features.

Methods And Findings: PCR-based assessments of the C9orf72 hexanucleotide repeat expansion in all study samples (including 82 FTD, 37 Alzheimer's disease (AD), and 16 other neurodegenerative/dementia disorder cases) were performed. Read More

View Article
December 2018

Gene mutations in a Han Chinese Alzheimer's disease cohort.

Brain Behav 2018 Dec 14:e01180. Epub 2018 Dec 14.

Department of Neurology, Xinxiang Medical University, Xinxiang, China.

Objective: Alzheimer's disease (AD) is the most common form of dementia characterized by memory loss at disease onset. The gene mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the frequent causes of AD. However, the clinical and genetic features of AD overlap with other neurodegenerative diseases. Read More

View Article
December 2018

Cognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders.

Ann Neurol 2018 Dec 14. Epub 2018 Dec 14.

Department of Neurology, Perelman School of Medicine at the University of Pennsylvania.

Objective: To use digital histology in a large autopsy cohort of Lewy Body Disorder (LBD) patients with dementia to test the hypotheses that co-occurring Alzheimer's disease (AD) pathology impacts the anatomic distribution of α-synuclein (SYN) pathology and that co-occurring neocortical tau pathology in LBD associates with worse cognitive performance and occurs in a pattern differing from AD.

Methods: Fifty-five autopsy-confirmed LBD (PDD: 36, DLB:19) patients and 25 AD patients were studied. LBD patients were categorized as having moderate/severe AD co-pathology (SYN+AD=20) or little/no AD co-pathology (SYN-AD=35). Read More

View Article
December 2018

Impaired Kv7 channel function in cerebral arteries of a tauopathy mouse model (rTg4510).

Physiol Rep 2018 Dec;6(23):e13920

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

In tauopathies, such as Alzheimer's disease with or without concomitant amyloid β plaques, cerebral arteries display pathological remodeling, leading to reduced brain tissue oxygenation and cognitive impairment. The precise mechanisms that underlie this vascular dysfunction remain unclear. Kv7 voltage-dependent K channels contribute to the development of myogenic tone in rat cerebral arteries. Read More

View Article
December 2018

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis A visual rating study.

Dement Neuropsychol 2018 Oct-Dec;12(4):388-393

Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.

Amyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS.

Objective: To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS. Read More

View Article
December 2018

Integrative system biology analyses of CRISPR-edited iPSC-derived neurons and human brains reveal deficiencies of presynaptic signaling in FTLD and PSP.

Transl Psychiatry 2018 Dec 13;8(1):265. Epub 2018 Dec 13.

Department of Psychiatry, Washington University School of Medicine, 660S. Euclid Ave. Campus Box 8134, St. Louis, MO, 63110, USA.

Mutations in the microtubule-associated protein tau (MAPT) gene cause autosomal dominant frontotemporal lobar degeneration with tau inclusions (FTLD-tau). MAPT p.R406W carriers present clinically with progressive memory loss and neuropathologically with neuronal and glial tauopathy. Read More

View Article
December 2018
1 Read

Presence of tau astrogliopathy in frontotemporal dementia caused by a novel Grn nonsense (Trp2*) mutation.

Neurobiol Aging 2018 Nov 20. Epub 2018 Nov 20.

Brain Tissue Bank, Fundación CIEN, Instituto de Salud Carlos III, Madrid, Spain.

Frontotemporal lobar degeneration caused by GRN mutations is mainly associated with a TDP-43 type A proteinopathy. We present a family with autosomal dominant frontotemporal lobar degeneration caused by a novel GRN nonsense mutation (c.5G>A: p. Read More

View Article
November 2018

Structural and metabolic cerebral alterations between elderly bipolar disorder and behavioural variant frontotemporal dementia: A combined MRI-PET study.

Aust N Z J Psychiatry 2018 Dec 13:4867418815976. Epub 2018 Dec 13.

1 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Background:: Elderly bipolar disorder (BD) and behavioural variant of frontotemporal dementia (bvFTD) may exhibit similar symptoms and both disorders are characterized by selective abnormalities in cortical and subcortical regions that are associated with cognitive and emotional impairments. We aimed to investigate common and distinct neural substrates of BD and bvFTD by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques.

Methods:: 3-Tesla MRI and 18 fluorodeoxyglucose-PET scans were acquired for 16 elderly BD patients, 23 bvFTD patients with mild cognitive impairments and 68 healthy controls (48 for PET and 20 for MRI analyses). Read More

View Article
December 2018

Identification of TCERG1 as a new genetic modulator of TDP-43 production in Drosophila.

Acta Neuropathol Commun 2018 Dec 12;6(1):138. Epub 2018 Dec 12.

Normandie University, UNIROUEN, Inserm, U1245, IRIB, Rouen, France.

TAR DNA-binding protein-43 (TDP-43) is a ubiquitously expressed DNA-/RNA-binding protein that has been linked to numerous aspects of the mRNA life cycle. Similar to many RNA-binding proteins, TDP-43 expression is tightly regulated through an autoregulatory negative feedback loop. Cell function and survival depend on the strict control of TDP-43 protein levels. Read More

View Article
December 2018

Quantitative analysis and EEG markers of KCNT1 epilepsy of infancy with migrating focal seizures.

Epilepsia 2018 Dec 7. Epub 2018 Dec 7.

INSERM Unit U1129 Infantile Epilepsies and Brain Plasticity, University Paris Descartes, Sorbonne Paris Cité, Paris, France.

Objective: We aimed to characterize epilepsy of infancy with migrating focal seizures (EIMFS), a rare, severe early onset developmental epilepsy related to KCNT1 mutation, and to define specific electroencephalography (EEG) markers using EEG quantitative analysis. The ultimate goal would be to improve early diagnosis and to better understand seizure onset and propagation of EIMFS as compared to other early onset developmental epilepsy.

Methods: EEG of 7 EIMFS patients with KCNT1 mutations (115 seizures) and 17 patients with other early onset epilepsies (30 seizures) was included in this study. Read More

View Article
December 2018

Clinical and Radiological Markers of Extra-Motor Deficits in Amyotrophic Lateral Sclerosis.

Front Neurol 2018 22;9:1005. Epub 2018 Nov 22.

Computational Neuroimaging Group, Academic Unit of Neurology, Trinity College Dublin, Dublin, Ireland.

Amyotrophic lateral sclerosis (ALS) is now universally recognized as a complex multisystem disorder with considerable extra-motor involvement. The neuropsychological manifestations of frontotemporal, parietal, and basal ganglia involvement in ALS have important implications for compliance with assistive devices, survival, participation in clinical trials, caregiver burden, and the management of individual care needs. Recent advances in neuroimaging have been instrumental in characterizing the biological substrate of heterogeneous cognitive and behavioral deficits in ALS. Read More

View Article
November 2018

Poly(ADP-ribose) engages the TDP-43 nuclear-localization sequence to regulate granulo-filamentous aggregation.

Biochemistry 2018 Dec 12. Epub 2018 Dec 12.

TAR DNA-binding protein of 43 kDa (TDP-43) forms granulo-filamentous aggregates in affected brain regions of >95% of patients with ALS and ~50% of patients with frontotemporal degeneration (FTD). Furthermore, in disease, TDP-43 becomes N-terminally truncated resulting in protein deposits that are mainly composed of the C-terminal prion-like domain (PrLD). The PrLD is inherently aggregation-prone and is hypothesized to drive protein aggregation of TDP-43 in disease. Read More

View Article
December 2018

The Functions of Prospection - Variations in Health and Disease.

Front Psychol 2018 27;9:2328. Epub 2018 Nov 27.

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

Much of human life revolves around anticipating and planning for the future. It has become increasingly clear that this capacity for is a core adaptive function of the mind. Here, we review the role of prospection in two key functional domains: goal-directed behavior and flexible decision-making. Read More

View Article
November 2018

Disease-associated tau impairs mitophagy by inhibiting Parkin translocation to mitochondria.

EMBO J 2018 Dec 11. Epub 2018 Dec 11.

Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia

Accumulation of the protein tau characterises Alzheimer's disease and other tauopathies, including familial forms of frontotemporal dementia (FTD) that carry pathogenic tau mutations. Another hallmark feature of these diseases is the accumulation of dysfunctional mitochondria. Although disease-associated tau is known to impair several aspects of mitochondrial function, it is still unclear whether it also directly impinges on mitochondrial quality control, specifically Parkin-dependent mitophagy. Read More

View Article
December 2018

Repetitive Behaviors in Frontotemporal Dementia: Compulsions or Impulsions?

J Neuropsychiatry Clin Neurosci 2018 Dec 12:appineuropsych18060148. Epub 2018 Dec 12.

From the Departments of Neurology (Moheb, Ashla, Mendez) and Psychiatry and Biobehavioral Sciences (Charuworn, Mendez), David Geffen School of Medicine, University of California at Los Angeles; and the Neurobehavior Unit, VA Greater Los Angeles Healthcare System, Los Angeles (Desarzant, Chavez, Mendez).

Objective:: The presence of repetitive behaviors is one of the core criteria for behavioral variant frontotemporal dementia (bvFTD). Patients with bvFTD often have perseverative, stereotyped, or compulsive-ritualistic behavior as an early aspect of their disorder. It is unclear whether such behaviors are related to compulsions, as in obsessive-compulsive disorder (OCD), or are part of the impulse disorder spectrum. Read More

View Article
December 2018

Prevalence of Depression, Anxiety and PTSD in People with Dementia: a Systematic Review and Meta-Analysis.

Neuropsychol Rev 2018 Dec 7. Epub 2018 Dec 7.

School of Psychology, Faculty of Health & Medical Sciences, University of Adelaide, Adelaide, South Australia, 5005, Australia.

There appears to be a link between depression/anxiety/PTSD and dementia, although the evidence is incomplete and the reason is unclear. Mental illness may cause dementia or may be prodromal or comorbid with dementia, or dementia may trigger a relapse of symptoms in individuals with a history of mental illness. This study examined the link between depression/anxiety/PTSD and dementia by evaluating the prevalence of these disorders in people with dementia, relative to their healthy peers. Read More

View Article
December 2018

Rare variants in patients with frontotemporal dementia and amyotrophic lateral sclerosis in a Chinese cohort.

Transl Neurodegener 2018 4;7:31. Epub 2018 Dec 4.

1Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008 China.

Background: The TANK-Binding Kinase 1 () gene has recently been identified as the third or fourth most frequent cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the genetic contribution of in a Chinese cohort.

Methods: A total of 270 cases with ALS, FTD, or their combination were recruited into this study. Read More

View Article
December 2018

Non-coding RNA in -related amyotrophic lateral sclerosis and frontotemporal dementia: A perfect storm of dysfunction.

Noncoding RNA Res 2018 Dec 10;3(4):178-187. Epub 2018 Sep 10.

Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Southampton, UK.

A hexanucleotide repeat expansion in the first intron/promoter region of is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both sense and antisense transcripts exist at the locus but the function of the antisense lncRNA is unknown. RNA toxicity of the transcribed repeat expansion has been implicated in the pathogenesis of -related ALS/FTD, not only through direct sequestration of important RNA binding proteins but also indirectly through non-ATG dependent translation into dipeptide repeats. Read More

View Article
December 2018

Inappropriate Laughter and Behaviours: How, What, and Why? Case of an Adult with Undiagnosed Gelastic Seizure with Hypothalamic Hamartoma.

Hawaii J Med Public Health 2018 Dec;77(12):319-324

John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI (NLB,JCK,AS).

Gelastic seizures (GS) are a rare form of epilepsy characterized by inappropriate, uncontrolled laughter. They are highly associated with abnormal cognitive development and behavioral problems in patients. Research has shown that GS can originate from hypothalamic hamartomas (HH), non- neoplastic masses consisting of gray matter with large and small neurons interspersed with glial nuclei. Read More

View Article
December 2018

Next Generation Sequencing Analysis in Early Onset Dementia Patients.

J Alzheimers Dis 2018 Dec 3. Epub 2018 Dec 3.

Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Background: Early onset dementias (EOD) are rare neurodegenerative dementias that present before 65 years. Genetic factors have a substantially higher pathogenetic contribution in EOD patients than in late onset dementia.

Objective: To identify known and/or novel rare variants in major candidate genes associated to EOD by high-throughput sequencing. Read More

View Article
December 2018
1 Read

Quality of Life in People with Young-Onset Dementia: A Nordic Two-Year Observational Multicenter Study.

J Alzheimers Dis 2018 Dec 1. Epub 2018 Dec 1.

Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.

Background: Cross-sectional studies of quality of life (QOL) of people with young-onset dementia shows diverging results.

Objective: To identify factors associated with QOL in people with young-onset Alzheimer's (AD) and frontotemporal dementia (FTD) and explore development in QOL over a two-year period, including differences between the two subtypes.

Methods: A two-year cohort study of 88 community-dwelling people with young-onset AD and FTD recruited from Nordic memory clinics. Read More

View Article
December 2018
1 Read

Spatiotemporal analysis for detection of pre-symptomatic shape changes in neurodegenerative diseases: Initial application to the GENFI cohort.

Neuroimage 2018 Dec 6. Epub 2018 Dec 6.

Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom; Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom.

Brain atrophy as measured from structural MR images, is one of the primary imaging biomarkers used to track neurodegenerative disease progression. In diseases such as frontotemporal dementia or Alzheimer's disease, atrophy can be observed in key brain structures years before any clinical symptoms are present. Atrophy is most commonly captured as volume change of key structures and the shape changes of these structures are typically not analysed despite being potentially more sensitive than summary volume statistics over the entire structure. Read More

View Article
December 2018
1 Read

Frontotemporal dementia spectrum: first genetic screen in a Greek cohort.

Neurobiol Aging 2018 Nov 3. Epub 2018 Nov 3.

Department of Psychiatry and Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address:

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative syndromes associated with several causative and susceptibility genes. Herein, we aimed to determine the incidence of the most common causative dementia genes in a cohort of 118 unrelated Greek FTD spectrum patients. We also screened for novel possible disease-associated variants in additional 21 genes associated with FTD or amyotrophic lateral sclerosis. Read More

View Article
November 2018

A Chemical Screen Identifies Compounds Limiting the Toxicity of C9ORF72 Dipeptide Repeats.

Cell Chem Biol 2018 Nov 5. Epub 2018 Nov 5.

Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 21 Stockholm, Sweden; Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain. Electronic address:

The expansion of GGGGCC repeats within the first intron of C9ORF72 constitutes the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Through repeat-associated non-ATG translation, these expansions are translated into dipeptide repeats (DPRs), some of which accumulate at nucleoli and lead to cell death. We here performed a chemical screen to identify compounds reducing the toxicity of ALS-related poly(PR) peptides. Read More

View Article
November 2018

TDP-43 accelerates deadenylation of target mRNAs by recruiting Caf1 deadenylase.

FEBS Lett 2018 Dec 6. Epub 2018 Dec 6.

Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.

TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein, whose loss-of-function mutation causes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Recent studies demonstrated that TDP-43 binds to the 3' UTR of target mRNAs to promote mRNA instability. Here, we show that TDP-43 recruits Caf1 deadenylase to mRNA targets and accelerates their deadenylation. Read More

View Article
December 2018
1 Read

A meta-analysis of neuropsychological, social cognitive, and olfactory functioning in the behavioral and language variants of frontotemporal dementia.

Psychol Med 2018 Dec 6:1-12. Epub 2018 Dec 6.

Department of Psychiatry and Behavioral Sciences,Baltimore, MD,USA.

Background: Though meta-analyses of neuropsychological and social cognitive deficits in behavioral variant frontotemporal dementia (bvFTD) have been conducted, no study has comprehensively characterized and compared the neuropsychological, social cognitive, and olfactory profiles in the behavioral and language variants of FTD.

Methods: Our search yielded 470 publications meeting inclusion criteria representing 11 782 FTD patients and 19 451 controls. For each domain, we calculated Hedges' g effect sizes, which represent the mean difference between the patient and control group divided by the pooled standard deviation. Read More

View Article
December 2018
4 Reads

Opposite subgenual cingulate cortical functional connectivity and metabolic activity patterns in refractory melancholic major depression.

Brain Imaging Behav 2018 Dec 5. Epub 2018 Dec 5.

Department of Psychiatry and Medical Psychology, Ghent University, C. Heymanslaan 10, 9000, Ghent, Belgium.

Although in treatment-resistant depression (TRD) subgenual anterior cingulate cortex (sgACC) functional connectivity (FC) is frequently used to examine deregulated brain networks, neurobiological data from other sources may be required to interpret these FC findings. In 16 melancholic TRD patients with a high level of treatment resistance and 16 closely matched healthy never-depressed individuals we verified whether sgACC FC patterns were related to regional metabolic activity (CMRglc) with FDG PET imaging. Notwithstanding that TRD patients displayed stronger sgACC FC with the right lateral frontotemporal cortex, metabolically they exhibited the opposite pattern. Read More

View Article
December 2018
1 Read

Modeling Parkinson's Disease and Atypical Parkinsonian Syndromes Using Induced Pluripotent Stem Cells.

Int J Mol Sci 2018 Dec 4;19(12). Epub 2018 Dec 4.

Department of Neurology, Fukuoka University, Fukuoka 814-0180, Japan.

Parkinson's disease (PD) and atypical parkinsonian syndromes are age-dependent multifactorial neurodegenerative diseases, which are clinically characterized by bradykinesia, tremor, muscle rigidity and postural instability. Although these diseases share several common clinical phenotypes, their pathophysiological aspects vary among the disease categories. Extensive animal-based approaches, as well as postmortem studies, have provided important insights into the disease mechanisms and potential therapeutic targets. Read More

View Article
December 2018
8 Reads

Longitudinal multimodal MRI as prognostic and diagnostic biomarker in presymptomatic familial frontotemporal dementia.

Brain 2018 Nov 30. Epub 2018 Nov 30.

Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.

Developing and validating sensitive biomarkers for the presymptomatic stage of familial frontotemporal dementia is an important step in early diagnosis and for the design of future therapeutic trials. In the longitudinal Frontotemporal Dementia Risk Cohort, presymptomatic mutation carriers and non-carriers from families with familial frontotemporal dementia due to microtubule-associated protein tau (MAPT) and progranulin (GRN) mutations underwent a clinical assessment and multimodal MRI at baseline, 2-, and 4-year follow-up. Of the cohort of 73 participants, eight mutation carriers (three GRN, five MAPT) developed clinical features of frontotemporal dementia ('converters'). Read More

View Article
November 2018
1 Read

Association of Cerebrospinal Fluid Neurofilament Light Protein Levels With Cognition in Patients With Dementia, Motor Neuron Disease, and Movement Disorders.

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

View Article
December 2018
1 Read

The applause sign in frontotemporal lobar degeneration and related conditions.

J Neurol 2018 Dec 1. Epub 2018 Dec 1.

Neurologische Klinik und Poliklinik, Ludwig Maximilians Universität München, Munich, Germany.

The applause sign, i.e., the inability to execute the same amount of claps as performed by the examiner, was originally reported as a sign specific for progressive supranuclear palsy (PSP). Read More

View Article
December 2018
1 Read
3.377 Impact Factor

Dural arteriovenous fistula mimicking temporal arteritis.

Clin Neurol Neurosurg 2018 Nov 26;176:44-46. Epub 2018 Nov 26.

Department of Neurosurgery, Kuala Lumpur Hospital, Malaysia.

Introduction: Dural arteriovenous fistula (dAVF) is a very rare disease characterized by an abnormal vascular communication between arteries and veins in dural mater. It frequently presents with intracranial haemorrhage. Common presenting symptoms are headache and seizures. Read More

View Article
November 2018
1 Read

Gray Matter Changes Associated With the Development of Delusions in Alzheimer Disease.

Am J Geriatr Psychiatry 2018 Oct 2. Epub 2018 Oct 2.

Keenan Research Centre for Biomedical Research (WQ, TAS, NWC, DGM, JJB, CEF), Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto; the Institute of Medical Sciences (WQ, TAS, TKR, CEF), University of Toronto, Toronto; Department of Psychiatry (CEF), Faculty of Medicine, University of Toronto, Toronto. Electronic address:

Objective: Delusions affect approximately a third of Alzheimer disease (AD) patients and are associated with poor outcomes. Previous studies investigating the neuroanatomic correlates of delusions have yet to reach a consensus, with findings of reduced volume across all lobes, particularly in frontal regions. The current study examined the gray matter (GM) differences associated with delusions in AD. Read More

View Article
October 2018
1 Read

Swedish Version of the Hayling Test: Clinical Utility in Frontotemporal Dementia Syndromes.

J Int Neuropsychol Soc 2018 Dec 3:1-9. Epub 2018 Dec 3.

4Clinical Memory Research Unit, Department of Clinical Sciences Malmö,Lund University,Lund,Sweden.

Objectives: The aim of this study was to assess the psychometric properties of a Swedish version of the Hayling test (HT-S) and its clinical utility in a group of patients with different frontotemporal dementia (FTD) syndromes. Early diagnosis of FTD is a challenge and requires a broad arsenal of assessment methods, neuropsychological tests not the least. The Hayling test assesses executive functions including initiation, efficiency and response inhibition. Read More

View Article
December 2018

Computational Investigation of RNA A-Bulges Related to Microtubule-Associated Protein Tau Causing Frontotemporal Dementia and Parkinsonism.

J Phys Chem B 2018 Dec 5. Epub 2018 Dec 5.

Mutations in the human tau gene result in alternative splicing of the tau protein, which cause frontotemporal dementia and Parkinsonism. One disease mechanism is linked to the stability of a hairpin within microtubule-associated protein tau (MAPT) mRNA, which contains an A-bulge. Here we employ computational methods to investigate the structural and thermodynamic properties of several A-bulge RNAs with different closing base-pairs. Read More

View Article
December 2018
2 Reads

Regulated proteolysis of p62/SQSTM1 enables differential control of autophagy and nutrient sensing.

Sci Signal 2018 Dec 4;11(559). Epub 2018 Dec 4.

Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK.

The multidomain scaffold protein p62 (also called sequestosome-1) is involved in autophagy, antimicrobial immunity, and oncogenesis. Mutations in , which encodes p62, are linked to hereditary inflammatory conditions such as Paget's disease of the bone, frontotemporal dementia (FTD), amyotrophic lateral sclerosis, and distal myopathy with rimmed vacuoles. Here, we report that p62 was proteolytically trimmed by the protease caspase-8 into a stable protein, which we called p62 We found that p62, but not full-length p62, was involved in nutrient sensing and homeostasis through the mechanistic target of rapamycin complex 1 (mTORC1). Read More

View Article
December 2018
1 Read

The Hairpin Form of r(GC) in c9ALS/FTD Is Repeat-Associated Non-ATG Translated and a Target for Bioactive Small Molecules.

Cell Chem Biol 2018 Nov 29. Epub 2018 Nov 29.

Departments of Chemistry and Neuroscience, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA. Electronic address:

The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an expanded GC repeat [(GC)] in C9ORF72. ALS/FTD-associated toxicity has been traced to the RNA transcribed from the repeat expansion [r(GC)], which sequesters RNA-binding proteins (RBPs) and undergoes repeat-associated non-ATG (RAN) translation to generate toxic dipeptide repeats. Using in vitro and cell-based assays, we identified a small molecule (4) that selectively bound r(GC), prevented sequestration of an RBP, and inhibited RAN translation. Read More

View Article
November 2018
1 Read

Moral judgment in patients with behavioral variant of frontotemporal dementia and amyotrophic lateral sclerosis: no impairment of the moral position, but rather its execution.

Amyotroph Lateral Scler Frontotemporal Degener 2018 Dec 4:1-7. Epub 2018 Dec 4.

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

Objective: To investigate moral judgment competence in patients with the behavioral variant frontotemporal dementia (bvFTD) compared to amyotrophic lateral sclerosis (ALS) and controls.

Methods: N = 12 bvFTD, N = 22 ALS patients and N = 19 neurological unimpaired controls were examined. In the 'Moral Competence Test' (MCT), participants had to evaluate two moral dilemmas by predefined arguments to measure the consistency of their moral judgments. Read More

View Article
December 2018
2 Reads

Neurons selectively targeted in frontotemporal dementia reveal early stage TDP-43 pathobiology.

Acta Neuropathol 2018 Dec 3. 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

View Article
December 2018
2 Reads

Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia.

Nat Med 2018 Dec 3. Epub 2018 Dec 3.

Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Identifying the mechanisms through which genetic risk causes dementia is an imperative for new therapeutic development. Here, we apply a multistage, systems biology approach to elucidate the disease mechanisms in frontotemporal dementia. We identify two gene coexpression modules that are preserved in mice harboring mutations in MAPT, GRN and other dementia mutations on diverse genetic backgrounds. Read More

View Article
December 2018
2 Reads

Disease-modifying effects of metabolic perturbations in ALS/FTLD.

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

View Article
December 2018
5 Reads

Aging and cerebrovascular lesions in pure and in mixed neurodegenerative and vascular dementia brains: a neuropathological study.

Folia Neuropathol 2018 ;56(2):81-87

Introduction: The prevalence of dementia is increasing in our aging population. Because of the complexity of disease pathology, dementia classifications remain controversial. The present post-mortem study investigates whether there are age differences between dementia brains with a single pure neurodegenerative or cerebrovascular disease and those with mixed pathological features. Read More

View Article
January 2018
1 Read

PD-linked CHCHD2 mutations impair CHCHD10 and MICOS complex leading to mitochondria dysfunction.

Hum Mol Genet 2018 Nov 29. Epub 2018 Nov 29.

Neuroscience Research laboratory, National Neuroscience Institute, Singapore.

CHCHD2 mutations were linked with autosomal dominant Parkinson's disease (PD) and recently, Alzheimer's disease/ Frontotemporal dementia. In current study, we generated isogenic human stem cell (hESC) lines harboring PD-associated CHCHD2 mutation R145Q or Q126X via CRISPR-Cas9 method, aiming to unravel pathophysiologic mechanism and seek potential intervention strategy against CHCHD2 mutant-caused defects. By engaging super resolution microscopy, we identified a physical proximity and similar distribution pattern of CHCHD2 along mitochondria with MICOS (mitochondrial inner membrane organizing system), a large protein complex maintaining mitochondria cristae. Read More

View Article
November 2018
6 Reads
6.393 Impact Factor

Frontotemporal dementia causative CHMP2B impairs neuronal endolysosomal traffic-rescue by TMEM106B knockdown.

Brain 2018 Dec;141(12):3428-3442

Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.

Mutations in the endosome-associated protein CHMP2B cause frontotemporal dementia and lead to lysosomal storage pathology in neurons. We here report that physiological levels of mutant CHMP2B causes reduced numbers and significantly impaired trafficking of endolysosomes within neuronal dendrites, accompanied by increased dendritic branching. Mechanistically, this is due to the stable incorporation of mutant CHMP2B onto neuronal endolysosomes, which we show renders them unable to traffic within dendrites. Read More

View Article
December 2018

Measurement of spinal cord atrophy using phase sensitive inversion recovery (PSIR) imaging in motor neuron disease.

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

View Article
November 2018
3 Reads

Facial expressiveness and physiological arousal in frontotemporal dementia: Phenotypic clinical profiles and neural correlates.

Cogn Affect Behav Neurosci 2018 Nov 28. Epub 2018 Nov 28.

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

Early theories of emotion processing propose an interplay between autonomic function and cognitive appraisal of emotions. Patients with frontotemporal dementia show profound social cognition deficits and atrophy in regions implicated in autonomic emotional responses (insula, amygdala, prefrontal cortex), yet objective measures of facial expressiveness and physiological arousal have been relatively unexplored. We investigated psychophysiological responses (surface facial electromyography (EMG); skin conductance level (SCL)) to emotional stimuli in 25 behavioural-variant frontotemporal dementia (bvFTD) patients, 14 semantic dementia (SD) patients, and 24 healthy older controls, while viewing emotionally positive, neutral, or negative video clips. Read More

View Article
November 2018
1 Read

Altered High Density Lipoprotein Composition in Behavioral Variant Frontotemporal Dementia.

Front Neurosci 2018 14;12:847. Epub 2018 Nov 14.

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

Frontotemporal dementia (FTD) is a common cause of early onset dementia with behavioral variant FTD (bvFTD) being the most common form. bvFTD is characterized clinically by behavioral and personality changes, eating abnormalities, and pathologically, by systemic lipid dysregulation that impacts on survival. As lipoprotein metabolism is at the core of lipid dysregulation, here, we analyzed the composition, both proteins and lipids, of the two major lipoprotein classes in blood - high density lipoproteins (HDLs) and low density lipoproteins (LDLs). Read More

View Article
November 2018
1 Read

ALS longitudinal studies with frequent data collection at home: study design and baseline data.

Amyotroph Lateral Scler Frontotemporal Degener 2018 Nov 28:1-7. Epub 2018 Nov 28.

b Department of Neurology , Barrow Neurological Institute , Phoenix , AZ , USA.

Objective: To design an ALS clinical study in which patients are remotely recruited, screened, enrolled and then assessed via daily data collection at home by themselves or caregivers.

Methods: This observational, natural-history study included two academic medical centers, one providing overall clinical management and the other overseeing computing and web-services design and management. Both healthy and ALS subjects were recruited on the Internet via advertisement on governmental and foundation websites as well as through Facebook and Google paid advertisements. Read More

View Article
November 2018

Perturbations in Traffic: Aberrant Nucleocytoplasmic Transport at the Heart of Neurodegeneration.

Cells 2018 Nov 26;7(12). Epub 2018 Nov 26.

Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.

Neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Huntington's disease (HD), are characterized by intracellular aggregation of proteins. In the case of ALS and FTD, these protein aggregates are found in the cytoplasm of affected neurons and contain certain RNA-binding proteins (RBPs), namely the TAR DNA-binding protein of 43 kDa (TDP-43) and the fused in sarcoma (FUS) gene product. TDP-43 and FUS are nuclear proteins and their displacement to the cytoplasm is thought to be adverse in at least two ways: loss-of-function in the nucleus and gain-of-toxicity in the cytoplasm. Read More

View Article
November 2018
6 Reads