7,941 results match your criteria Frontotemporal Lobe Dementia


An Intramolecular Salt Bridge Linking TDP43 RNA Binding, Protein Stability, and TDP43-Dependent Neurodegeneration.

Cell Rep 2019 Apr;27(4):1133-1150.e8

Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI 48104, USA; Department of Neurology, University of Michigan, Ann Arbor, MI 48104, USA; Neuroscience Graduate Program, Department of Pharmacology, University of Michigan, Ann Arbor, MI 48104, USA. Electronic address:

The majority of individuals with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) exhibit neuronal cytoplasmic inclusions rich in the RNA binding protein TDP43. Even so, the relation between the RNA binding properties of TDP43 and neurodegeneration remains obscure. Here, we show that engineered mutations disrupting a salt bridge between the RNA recognition motifs of TDP43 interfere with RNA binding and eliminate the recognition of native TDP43 substrates. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.093DOI Listing

A review on shared clinical and molecular mechanisms between bipolar disorder and frontotemporal dementia.

Prog Neuropsychopharmacol Biol Psychiatry 2019 Apr 20. Epub 2019 Apr 20.

Bipolar Disorder Program (PROMAN), Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil.

Mental disorders are highly prevalent and important causes of medical burden worldwide. Co-occurrence of neurological and psychiatric symptoms are observed among mental disorders, representing a challenge for their differential diagnosis. Psychiatrists and neurologists have faced challenges in diagnosing old adults presenting behavioral changes. Read More

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http://dx.doi.org/10.1016/j.pnpbp.2019.04.008DOI Listing

Differential insular cortex sub-regional atrophy in neurodegenerative diseases: a systematic review and meta-analysis.

Brain Imaging Behav 2019 Apr 23. Epub 2019 Apr 23.

Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, De Boelelaan 1108, 1081 HZ, Amsterdam, Netherlands.

The insular cortex is proposed to function as a central brain hub characterized by wide-spread connections and diverse functional roles. As a result, its centrality in the brain confers high metabolic demands predisposing it to dysfunction in disease. However, the functional profile and vulnerability to degeneration varies across the insular sub-regions. Read More

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http://dx.doi.org/10.1007/s11682-019-00099-3DOI Listing

Next Generation Precision Medicine: CRISPR-mediated Genome Editing for the Treatment of Neurodegenerative Disorders.

J Neuroimmune Pharmacol 2019 Apr 23. Epub 2019 Apr 23.

Department of Neurology, Center for Translational Neuroscience, School of Medicine, University of Missouri, M741A Medical Science Building, 1 Hospital Drive, Columbia, MO, 65211, USA.

Despite significant advancements in the field of molecular neurobiology especially neuroinflammation and neurodegeneration, the highly complex molecular mechanisms underlying neurodegenerative diseases remain elusive. As a result, the development of the next generation neurotherapeutics has experienced a considerable lag phase. Recent advancements in the field of genome editing offer a new template for dissecting the precise molecular pathways underlying the complex neurodegenerative disorders. Read More

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http://dx.doi.org/10.1007/s11481-019-09849-yDOI Listing

Financial capacity in frontotemporal dementia and related presentations.

J Neurol 2019 Apr 22. Epub 2019 Apr 22.

Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Parkwood Institute, Lawson Health Research Institute, University of Western Ontario, 550 Wellington Rd, London, ON, Canada.

Background: Changes in financial judgement and skills can herald a neurodegenerative dementia and are a common reason for referral for cognitive neurologic assessment. However, patients with neurodegenerative diseases affecting the frontal or temporal lobes may perform well on standard cognitive tests, complicating clinical determinations about their diagnosis and financial capacity.

Methods: Forty-five patients with possible or probable FTD or Alzheimer's disease and 22 healthy controls completed two financial assessment batteries, the FACT and the FCAI. Read More

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http://link.springer.com/10.1007/s00415-019-09317-w
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http://dx.doi.org/10.1007/s00415-019-09317-wDOI Listing
April 2019
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Citalopram Improves Obsessive-Compulsive Crossword Puzzling in Frontotemporal Dementia.

Case Rep Neurol 2019 Jan-Apr;11(1):94-105. Epub 2019 Mar 19.

Neurology Department, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.

Behavioral variant frontotemporal dementia (bvFTD) is characterized by severe changes in personality/behavior. Recent studies have provided evidence that a decrease in serotonin receptors and neuronal loss in the raphe nuclei play a role in the bvFTD pathology. Serotonergic antidepressants have been reported to diminish behavioral disturbances in bvFTD, particularly repetitive behaviors, disinhibition, apathy, sexually inappropriate behaviors, and hyperorality. Read More

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http://dx.doi.org/10.1159/000495561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465705PMC

Topographic distribution of white matter changes and lacunar infarcts in neurodegenerative and vascular dementia syndromes: A post-mortem 7.0-tesla magnetic resonance imaging study.

Eur Stroke J 2016 Jun 18;1(2):122-129. Epub 2016 May 18.

Université Lille 2, INSERM U 1171, Lille, France.

Background: White matter changes and lacunar infarcts are regarded as linked to the same underlying small-vessel pathology. On magnetic resonance imaging, white matter changes are frequently observed, while the number of lacunar infarcts is probably underestimated. The present study post-mortem 7. Read More

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http://dx.doi.org/10.1177/2396987316650780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301232PMC

Schizoaffective disorder comorbid with type 2 diabetes mellitus accompanied by frontotemporal atrophy and impaired cognition: A CARE compliant case report.

Medicine (Baltimore) 2019 Apr;98(16):e15292

Department of Affective Disorder, Shenzhen Kangning Hospital, Luohu District, Shenzhen, China.

Rationale: Brain atrophy coupled with impaired cognition may be a sign of dementia. However, growing evidence indicates that schizoaffective disorder (SAD) and type 2 diabetes mellitus (T2DM) play roles in the processes of frontotemporal atrophy and cognitive decline. Few cases of frontotemporal atrophy and impaired cognition have been reported in young adult patients with SAD and T2DM. Read More

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http://dx.doi.org/10.1097/MD.0000000000015292DOI Listing
April 2019
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Disruption of valosin-containing protein activity causes cardiomyopathy and reveals pleiotropic functions in cardiac homeostasis.

J Biol Chem 2019 Apr 21. Epub 2019 Apr 21.

Dept Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, United States.

Valosin-Containing Protein (VCP), also known as p97, is an ATPase with diverse cellular functions, although the most highly characterized is the targeting of misfolded or aggregated proteins to degradation pathways, including the endoplasmic reticulum-associated degradation (ERAD) pathway. However, how VCP functions in the heart has not been carefully examined despite the fact that human mutations in VCP causes Paget disease of bone and frontotemporal dementia, an autosomal dominant multisystem proteinopathy that includes disease in the heart, skeletal muscle, brain, and bone. Here, we generated cardiac-specific transgenic mice overexpressing wildtype VCP or a VCP-K524A mutant with deficient ATPase activity. Read More

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http://dx.doi.org/10.1074/jbc.RA119.007585DOI Listing

Tauopathy in the periaqueductal gray, kölliker-fuse nucleus and nucleus retroambiguus is not predicted by ultrasonic vocalization in tau-P301L mice.

Behav Brain Res 2019 Apr 17:111916. Epub 2019 Apr 17.

The Florey Institute of Neuroscience and Mental Health, Discovery Neuroscience theme, Australia. Electronic address:

Upper airway and vocalization control areas such as the periaqueductal gray (PAG), kölliker-fuse nucleus (KF) and nucleus retroambiguus (NRA) are prone to developing tauopathy in mice expressing the mutant human tau P301 L protein. Consequently, impaired ultrasonic vocalization (USV) previously identified in tau-P301 L mice at the terminal disease stage of 8-9 months of age, was attributed to the presence of tauopathy in these regions. Our aim was to establish whether the onset of USV disorders manifest prior to the terminal stage, and if USV disorders are predictive of the presence of tauopathy in the PAG, KF and NRA. Read More

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http://dx.doi.org/10.1016/j.bbr.2019.111916DOI Listing

Dopamine receptor D (DRD) polymorphisms with reduced functional potency intensify atrophy in syndrome-specific sites of frontotemporal dementia.

Neuroimage Clin 2019 Apr 10;23:101822. Epub 2019 Apr 10.

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

Objective: We aimed to understand the impact of dopamine receptor D (DRD) polymorphisms on neurodegeneration in patients with dementia. We hypothesized that DRDdampened-variants with reduced functional potency would be associated with greater atrophy in regions with higher receptor density. Given that DRD is concentrated in anterior regions of the limbic and cortical forebrain we anticipated genotype effects in patients with a more rostral pattern of neurodegeneration. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475809PMC

White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis.

Neuropathol Appl Neurobiol 2019 Apr 19. Epub 2019 Apr 19.

Department of Anatomy, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.

Objective: The aim of this study was to test the hypothesis that white matter degeneration of the perforant path - as part of the Papez circuit - is a key feature of amyotrophic lateral sclerosis (ALS), even in the absence of frontotemporal dementia (FTD) or deposition of pTDP-43 inclusions in hippocampal granule cells.

Methods: We used diffusion MRI (dMRI), polarized light imaging (PLI) and immunohistochemical analysis of post-mortem hippocampus specimens from controls (n=5) and ALS patients (n=14) to study white matter degeneration in the perforant path.

Results: dMRI demonstrated a decrease in fractional anisotropy (p=0. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/nan.12555
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http://dx.doi.org/10.1111/nan.12555DOI Listing
April 2019
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Promising therapies for the treatment of frontotemporal dementia clinical phenotypes: from symptomatic to disease-modifying drugs.

Expert Opin Pharmacother 2019 Apr 19:1-17. Epub 2019 Apr 19.

a Neurodegenerative Disease Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs , University of Bari "Aldo Moro" , Bari , Italy.

Introduction: Frontotemporal dementia (FTD) is a heterogeneous clinical entity that includes several disorders characterized by different cellular mechanisms. Distinctive clinical features in FTD include behavioral, affective, and cognitive symptoms. Unfortunately, little progress has been made over the past 20 years in terms of the development of effective disease-modifying drugs with the currently available symptomatic treatments having limited clinical utility. Read More

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http://dx.doi.org/10.1080/14656566.2019.1598377DOI Listing

The olfactory bulb proteotype differs across frontotemporal dementia spectrum.

J Proteomics 2019 Apr 15;201:37-47. Epub 2019 Apr 15.

Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea, 3, 31008 Pamplona, Spain; Proteored-ISCIII, Proteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Irunlarrea 3, 31008 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain, Irunlarrea 3, 31008 Pamplona, Spain. Electronic address:

Mild olfactory dysfunction has been observed in frontotemporal dementias (FTD). However, the underlying molecular mechanisms associated to this deficit are poorly understood. We applied quantitative proteomics to analyze pathological effects on the olfactory bulb (OB) from progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration (FTLD-TDP43) subjects respect to elderly non-FTD group. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S18743919193011
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http://dx.doi.org/10.1016/j.jprot.2019.04.011DOI Listing
April 2019
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Clinical and Genetic Study of the First Japanese FTDP-17 Patient with a Mutation of +3 in Intron 10 in the MAPT Gene.

Intern Med 2019 Apr 17. Epub 2019 Apr 17.

Department of Neurology, Graduate School of Medical Sciences, University of Yamanashi, Japan.

Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) with mutations in the MAPT gene is a hereditary neurodegenerative tauopathy with various clinical phenotypes. We herein report the first Japanese patient with FTDP-17 caused by an IVS10+3G>A mutation in the MAPT gene, which is linked to an H1M haplotype. The present study suggests that the IVS10+3G>A mutation in the MAPT gene can have originated from a non-Caucasian population. Read More

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https://www.jstage.jst.go.jp/article/internalmedicine/advpub
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http://dx.doi.org/10.2169/internalmedicine.2761-19DOI Listing
April 2019
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Confirmation of high frequency of C9orf72 mutations in patients with frontotemporal dementia from Sweden.

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

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.03.009DOI Listing
March 2019
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F-Flortaucipir in TDP-43 associated frontotemporal dementia.

Sci Rep 2019 Apr 15;9(1):6082. Epub 2019 Apr 15.

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

Retention of F-Flortaucipir is reportedly increased in the semantic variant of primary progressive aphasia (svPPA), which is dominated by TDP-43 pathology. However, it is unclear if F-Flortaucipir is also increased in other TDP-43 diseases, such as bvFTD caused by a C9orf72 gene mutation. We therefore recruited six C9orf72 expansion carriers, six svPPA patients, and 54 healthy controls. Read More

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http://dx.doi.org/10.1038/s41598-019-42625-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465310PMC
April 2019
2 Reads

Toward a Glutamate Hypothesis of Frontotemporal Dementia.

Front Neurosci 2019 29;13:304. Epub 2019 Mar 29.

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

Frontotemporal dementia (FTD) is a heterogenous neurodegenerative disorder, characterized by diverse clinical presentations, neuropathological characteristics and underlying genetic causes. Emerging evidence has shown that FTD is characterized by a series of changes in several neurotransmitter systems, including serotonin, dopamine, GABA and, above all, glutamate. Indeed, several studies have now provided preclinical and clinical evidence that glutamate is key in the pathogenesis of FTD. Read More

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https://www.frontiersin.org/article/10.3389/fnins.2019.00304
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http://dx.doi.org/10.3389/fnins.2019.00304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449454PMC
March 2019
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Burden of caregivers of patients with frontotemporal lobar degeneration - a scoping review.

Int Psychogeriatr 2019 Apr 15:1-21. Epub 2019 Apr 15.

German Center for Neurodegenerative Diseases (DZNE),Greifswald,Germany.

ABSTRACTBackground:Frontotemporal lobar degeneration (FTLD) is the second-most common cause of young-onset dementia. Personality and behavior changes lead to high caregiver stress and burden, but little support is available. Our aim is to present the evidence on the characteristics, challenges and unmet needs of caregivers as well as on possible interventions. Read More

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http://dx.doi.org/10.1017/S1041610219000176DOI Listing
April 2019
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Searching for novel cerebrospinal fluid biomarkers of tau pathology in frontotemporal dementia: an elusive quest.

J Neurol Neurosurg Psychiatry 2019 Apr 13. Epub 2019 Apr 13.

Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK

Background: Frontotemporal dementia (FTD) is a pathologically heterogeneous neurodegenerative disorder associated usually with tau or TDP-43 pathology, although some phenotypes such as logopenic variant primary progressive aphasia are more commonly associated with Alzheimer's disease pathology. Currently, there are no biomarkers able to diagnose the underlying pathology during life. In this study, we aimed to investigate the potential of novel tau species within cerebrospinal fluid (CSF) as biomarkers for tau pathology in FTD. Read More

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http://dx.doi.org/10.1136/jnnp-2018-319266DOI Listing
April 2019
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Molecular dynamics study of structure, folding, and aggregation of poly-glycine-alanine (Poly-GA).

J Chem Phys 2019 Apr;150(14):144307

Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-1211, USA.

Poly-glycine-alanine (poly-GA) proteins are widely believed to be one of the main toxic dipeptide repeat molecules associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia diseases. Using discontinuous molecular dynamics simulation and an all-atom model of the proteins, we study folding, stability, and aggregation of poly-GA. The results demonstrate that poly-GA is an aggregation-prone protein that, after a long enough time, forms β-sheet-rich aggregates that match recent experiment data and that two unique helical structures are formed very frequently, namely, β-helix and double-helix. Read More

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http://dx.doi.org/10.1063/1.5081867DOI Listing
April 2019
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Machine learning based hierarchical classification of frontotemporal dementia and Alzheimer's disease.

Neuroimage Clin 2019 Apr 3;23:101811. Epub 2019 Apr 3.

Department of Bio-convergence Engineering, Korea University, Seoul, Republic of Korea; School of Biomedical Engineering, Korea University, Seoul, Republic of Korea. Electronic address:

Background: In a clinical setting, an individual subject classification model rather than a group analysis would be more informative. Specifically, the subtlety of cortical atrophy in some frontotemporal dementia (FTD) patients and overlapping patterns of atrophy among three FTD clinical syndromes including behavioral variant FTD (bvFTD), non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), and semantic variant PPA (svPPA) give rise to the need for classification models at the individual level. In this study, we aimed to classify each individual subject into one of the diagnostic categories in a hierarchical manner by employing a machine learning-based classification method. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458431PMC
April 2019
2 Reads

Incidence of frontotemporal lobar degeneration in Italy: The Salento-Brescia Registry study.

Neurology 2019 Apr 12. Epub 2019 Apr 12.

From the Center for Neurodegenerative Diseases and the Aging Brain (G.L., M.P., C.Z., R.C., R. Tortelli, P.B., R.B.), Department of Clinical Research in Neurology, and Department of Basic Medical Sciences, Neuroscience and Sense Organs (G.L., M.P., P.B.), University of Bari "Aldo Moro"; "Pia Fondazione Cardinale G. Panico" (G.L., M.P., C.Z., R.C., R. Tortelli, P.B., R.B.), Tricase, Lecce; IRCCS Centro San Giovanni di Dio Fatebenefratelli (G.B., S.F., L.B., R.G., S.F.C.); Department of Clinical and Experimental Sciences (R. Turrone, A.P., A.A., B.B.), Neurology Unit, University of Brescia; Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA) (P.B.), University of Firenze; and Department of Neurology (E.B.), Ospedali Riuniti, Foggia, Italy.

Objective: The goal of the present work, based on a collaborative research registry in Italy (the Salento-Brescia Registry), was to assess the incidence of frontotemporal lobar degeneration (FTLD) and to define the frequencies of different FTLD phenotypes in the general population.

Methods: The study was conducted from January 1, 2017, to December 31, 2017, in 2 Italian provinces: Lecce (in Puglia) in the south (area 2,799.07 km, inhabitants 802,082) and Brescia (in Lombardy) in the north (area 4,785. Read More

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http://www.neurology.org/lookup/doi/10.1212/WNL.000000000000
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http://dx.doi.org/10.1212/WNL.0000000000007498DOI Listing
April 2019
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C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition.

Neurobiol Aging 2019 Mar 11. Epub 2019 Mar 11.

Molecular Neurology, Research Programs Unit, Department of Neurology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.02.026DOI Listing
March 2019
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TMEM106B Effect on Cognition in Parkinson's Disease and Frontotemporal Dementia.

Ann Neurol 2019 Apr 11. Epub 2019 Apr 11.

Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Objective: Common variants near TMEM106B associate with risk of developing frontotemporal dementia (FTD). Emerging evidence suggests a role for TMEM106B in neurodegenerative processes beyond FTD. The objective of this study is to evaluate the effect of TMEM106B genotype on cognitive decline across multiple neurogenerative diseases. Read More

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http://dx.doi.org/10.1002/ana.25486DOI Listing
April 2019
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Disease-modifying therapies for tauopathies: agents in the pipeline.

Expert Rev Neurother 2019 Apr 11. Epub 2019 Apr 11.

g Department of Neurological Sciences , Santa Maria University Hospital , Terni , Italy.

Introduction: Tauopathies are heterogeneous clinicopathological entities characterized by abnormal neuronal and/or glial inclusions of the microtubule-binding protein tau. Primary tauopathies considered to be diseases correspond to a major class of frontotemporal lobar degeneration (FTLD) neuropathology (FTLD-Tau), including several forms of frontotemporal dementia (FTD) clinical syndromes. Little progress has been made in the past 20 years in developing effective disease-modifying drugs for primary tauopathies and available symptomatic treatments have limited efficacy. Read More

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http://dx.doi.org/10.1080/14737175.2019.1606715DOI Listing
April 2019
2 Reads
2.834 Impact Factor

Aberrant Phase Transitions: Side Effects and Novel Therapeutic Strategies in Human Disease.

Front Genet 2019 22;10:173. Epub 2019 Mar 22.

University of Rome "Foro Italico", Rome, Italy.

Phase separation is a physiological process occurring spontaneously when single-phase molecular complexes separate in two phases, a concentrated phase and a more diluted one. Eukaryotic cells employ phase transition strategies to promote the formation of intracellular territories not delimited by membranes with increased local RNA concentration, such as nucleolus, paraspeckles, P granules, Cajal bodies, P-bodies, and stress granules. These organelles contain both proteins and coding and non-coding RNAs and play important roles in different steps of the regulation of gene expression and in cellular signaling. Read More

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http://dx.doi.org/10.3389/fgene.2019.00173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440380PMC
March 2019
2 Reads

Predicting the future of ALS: the impact of demographic change and potential new treatments on the prevalence of ALS in the United Kingdom, 2020-2116.

Amyotroph Lateral Scler Frontotemporal Degener 2019 Apr 9:1-11. Epub 2019 Apr 9.

a Department of Basic and Clinical Neuroscience , King's College London, Maurice Wohl Clinical Neuroscience Institute , London , UK.

Objective: To model the effects of demographic change under various scenarios of possible future treatment developments in ALS.

Methods: Patients diagnosed with ALS at the King's College Hospital Motor Nerve Clinic between 2004 and 2017, and living within the London boroughs of Lambeth, Southwark, and Lewisham (LSL), were included as incident cases. We also ascertained incident cases from the Canterbury region over the same period. Read More

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http://dx.doi.org/10.1080/21678421.2019.1587629DOI Listing
April 2019
4 Reads

Clinical Effects of Frontal Behavioral Impairment: Cortical Thickness and Cognitive Decline in Individuals with Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment.

J Alzheimers Dis 2019 Apr 1. Epub 2019 Apr 1.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background: Frontal behavioral impairment (FrBI) is commonly observed in various degenerative diseases and refers to various behavioral symptoms.

Objective: We investigated the effects of the presence of FrBI on cortical thickness, and the longitudinal neuropsychological changes in people in the predementia stage.

Methods: A total of 794 individuals completed neuropsychological tests and the Frontal Behavioral Inventory (FBI) Questionnaire, and underwent magnetic resonance (MR) scanning. Read More

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http://dx.doi.org/10.3233/JAD-190007DOI Listing
April 2019
3 Reads

A cortical microvascular structure in vascular dementia, Alzheimer's disease, frontotemporal lobar degeneration, and non-demented controls: a sign of angiogenesis due to brain ischaemia?

Neuropathol Appl Neurobiol 2019 Apr 8. Epub 2019 Apr 8.

Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Sweden.

Aims: We observed a microvascular structure in the cerebral cortex that has not, to our knowledge, been previously described. We have termed the structure a 'raspberry', referring to its appearance under a bright-field microscope. We hypothesised that raspberries form through angiogenesis due to some form of brain ischaemia or hypoperfusion. Read More

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http://dx.doi.org/10.1111/nan.12552DOI Listing
April 2019
1 Read

Distal myopathy and rapidly progressive dementia associated with a novel mutation in the VCP gene: Expanding inclusion body myopathy with early-onset Paget disease and frontotemporal dementia spectrum.

J Clin Neurosci 2019 Apr 4. Epub 2019 Apr 4.

Department of Neurosciences and Mental Health, Centro Hospitalar Universitário de Lisboa-Norte, Lisbon, Portugal; Instituto de Medicina Molecular and Instituto de Fisiologia, Faculdade de Medicina, Universidade de Lisboa, Portugal.

Distal myopathies are a clinically and genetically heterogeneous group characterized by distal weakness at onset. Distal myopathies are classified according to age of onset, inheritance pattern, clinical features and molecular diagnosis. Inclusion body myopathy with early-onset Paget disease and fronto-temporal dementia is a rare adult late-onset disease related to valosin-containing protein gene mutations with an autosomal dominance inheritance. Read More

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http://dx.doi.org/10.1016/j.jocn.2019.03.063DOI Listing
April 2019
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Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer's disease.

J Psychiatr Res 2019 Mar 30;113:141-147. Epub 2019 Mar 30.

Center for Neurodegenerative Diseases, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing, 100050, China; Parkinson's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100050, China. Electronic address:

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. It shares clinical and pathological features with other types of dementia, such as vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD). We have hypothesized that there might be an overlapping molecular mechanism and genetic basis to the different types of dementia. Read More

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http://dx.doi.org/10.1016/j.jpsychires.2019.03.026DOI Listing

Neurofilament light chain as a blood biomarker to differentiate psychiatric disorders from behavioural variant frontotemporal dementia.

J Psychiatr Res 2019 Mar 24;113:137-140. Epub 2019 Mar 24.

Department of Neurology, Ulm University, Ulm, Germany. Electronic address:

The overlapping symptoms of behavioural variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (such as depressive disorder, schizophrenia spectrum, and bipolar disorder) present a challenge for the differential diagnosis of bvFTD in middle and older-aged people. Neurofilaments are cytoskeletal proteins in the neurons, and several studies have reported elevated levels of neurofilament light chain (NfL) in cerebrospinal fluid of neurodegenerative as well as psychiatric disorders. The study aims to determine the utility of serum NfL levels as a biomarker to differentiate between bvFTD and psychiatric disorder. Read More

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http://dx.doi.org/10.1016/j.jpsychires.2019.03.019DOI Listing
March 2019
8 Reads
3.957 Impact Factor

Diagnostic accuracy of frontotemporal dementia. An artificial intelligence-powered study of symptoms, imaging and clinical judgement.

Adv Med Sci 2019 Apr 1;64(2):292-302. Epub 2019 Apr 1.

Bristol Institute of Clinical Neurosciences, University of Bristol, Southmead Hospital, Bristol, UK.

Purpose: Frontotemporal dementia (FTD) is a neurodegenerative disorder associated with a poor prognosis and a substantial reduction in quality of life. The rate of misdiagnosis of FTD is very high, with patients often waiting for years without a firm diagnosis. This study investigates the current state of the misdiagnosis of FTD using a novel artificial intelligence-based algorithm. Read More

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http://dx.doi.org/10.1016/j.advms.2019.03.002DOI Listing
April 2019
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ApoE4 lowers age at onset in patients with frontotemporal dementia and tauopathy independent of amyloid-β copathology.

Alzheimers Dement (Amst) 2019 Dec 19;11:277-280. Epub 2019 Mar 19.

UCL Institute of Prion Diseases, London, UK.

Introduction: Apolipoprotein E (ApoE) is the most important genetic risk factor for Alzheimer's disease (AD), with ApoE4 thought to enhance and accelerate amyloid-β (Aβ) pathology. ApoE4 has recently been described to increase neurodegeneration in a mouse model of frontotemporal dementia (FTD), , and in patients, demonstrating that ApoE4 modifies tauopathy independently of Aβ. This raises the question whether ApoE genotype also modifies the clinical phenotype in patients with FTD with tau pathology. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S23528729193001
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http://dx.doi.org/10.1016/j.dadm.2019.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430720PMC
December 2019
3 Reads

EEG Analysis and Spect Imaging in Alzheimer's Disease, Vascular Dementia and Mild Cognitive Impairment.

Psychiatr Danub 2019 Mar;31(1):111-115

Department of Neurology, University Hospital Center Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia,

Background: Alzheimer's disease (AD) and vascular dementia (VaD) represent a leading public-health problem given the rising age of the population. Early diagnosis of dementia, especially at the stage of mild cognitive impairment (MCI) has become an important goal of the modern patient work-up. Brain perfusion single-photon emission computed tomography (SPECT) has become a mainstay of diagnostic algorithms in patients with dementia showing specific patterns of hypoperfusion in temporal and parietal lobes. Read More

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http://dx.doi.org/10.24869/psyd.2019.111DOI Listing
March 2019
2 Reads

Phase separation of RNA-binding proteins in physiology and disease: An introduction to the JBC Reviews thematic series.

Authors:
James Shorter

J Biol Chem 2019 04 4. Epub 2019 Apr 4.

University of Pennsylvania, United States.

In recent years, there has been a jarring awakening that liquid-liquid phase separation (LLPS) of key protein and nucleic acid scaffolds underpins the biogenesis of diverse membraneless organelles, including P granules and stress granules in the cytoplasm, and, nucleoli and paraspeckles in the nucleus. These biomolecular condensates are proposed to be critical organizers of subcellular biochemistry and to control the flow of information from genotype to phenotype. Despite clear biological utility, LLPS can also have deleterious outcomes. Read More

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http://www.jbc.org/lookup/doi/10.1074/jbc.REV119.007944
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http://dx.doi.org/10.1074/jbc.REV119.007944DOI Listing
April 2019
4 Reads

ADAR2 mislocalization and widespread RNA editing aberrations in C9orf72-mediated ALS/FTD.

Acta Neuropathol 2019 Apr 3. Epub 2019 Apr 3.

Department of Neurobiology, Barrow Neurological Institute, 350 W Thomas Road, Phoenix, AZ, 85013, USA.

The hexanucleotide repeat expansion GGGGCC (GC) in the C9orf72 gene is the most common genetic abnormality associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent findings suggest that dysfunction of nuclear-cytoplasmic trafficking could affect the transport of RNA binding proteins in C9orf72 ALS/FTD. Here, we provide evidence that the RNA editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) is mislocalized in C9orf72 repeat expansion mediated ALS/FTD. Read More

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http://dx.doi.org/10.1007/s00401-019-01999-wDOI Listing

Longitudinal F-FDG PET and MRI Reveal Evolving Imaging Pathology That Corresponds to Disease Progression in a Patient With ALS-FTD.

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

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http://dx.doi.org/10.3389/fneur.2019.00234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433744PMC
March 2019
3 Reads

The Role of the Right Hemisphere in Emotional and Behavioral Disorders of Patients With Frontotemporal Lobar Degeneration: An Updated Review.

Authors:
Guido Gainotti

Front Aging Neurosci 2019 19;11:55. Epub 2019 Mar 19.

Institute of Neurology of the IRCCS Fondazione Policlinico Gemelli, Catholic University of Rome, Rome, Italy.

Two main models have been advanced to explain the asymmetries observed in the representation and processing of emotions. The first model, labeled "the right hemisphere hypothesis," assumes a general dominance of the right hemisphere for all emotions, regardless of affective valence. The second model, named "the valence hypothesis," assumes an opposite dominance of the left hemisphere for positive emotions and the right hemisphere for negative emotions. Read More

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http://dx.doi.org/10.3389/fnagi.2019.00055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433967PMC
March 2019
2 Reads

Retinoic acid worsens ATG10-dependent autophagy impairment in TBK1-mutant hiPSC-derived motoneurons through SQSTM1/p62 accumulation.

Autophagy 2019 Apr 2:1-19. Epub 2019 Apr 2.

a Institute of Anatomy and Cell Biology , Ulm University , Ulm , DE , Germany.

Mutations in the TBK1 (TANK binding kinase 1) gene are causally linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TBK1 phosphorylates the cargo receptors OPTN and SQSTM1 regulating a critical step in macroautophagy/autophagy. Disruption of the autophagic flux leads to accumulation of cytosolic protein aggregates, which are a hallmark of ALS. Read More

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http://dx.doi.org/10.1080/15548627.2019.1589257DOI Listing
April 2019
3 Reads
11.753 Impact Factor

Phenocopy syndrome of behavioral variant frontotemporal dementia: a systematic review.

Alzheimers Res Ther 2019 Apr 1;11(1):30. Epub 2019 Apr 1.

Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Instituto de Ciências Biológicas (sala 100, Bloco M1), Avenida Presidente Antônio Carlos, 6627 - Pampulha, Belo Horizonte, MG, 31270-010, Brazil.

Background: The phenocopy syndrome of behavioral variant of frontotemporal dementia (phFTD) refers to patients presenting with neuropsychiatric symptoms mimicking the behavioral variant frontotemporal dementia (bvFTD), but lacking frontotemporal atrophy/hypometabolism on neuroimaging and not evolving to dementia during the follow-up. It is important to recognize phFTD for clinical and research purposes.

Objective: The aim of this study was to perform a systematic review of the available literature on phFTD taking into account its clinical, cognitive, imaging, genetic, and pathological features. Read More

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https://alzres.biomedcentral.com/articles/10.1186/s13195-019
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http://dx.doi.org/10.1186/s13195-019-0483-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444822PMC
April 2019
3 Reads

Telomere length is greater in ALS than in controls: a whole genome sequencing study.

Amyotroph Lateral Scler Frontotemporal Degener 2019 Apr 1:1-6. Epub 2019 Apr 1.

a Department of Basic and Clinical Neuroscience , King's College London, Maurice Wohl Clinical Neuroscience Institute , London , UK.

Background: Amyotrophic lateral sclerosis is a neurodegenerative disease of motor neurons resulting in progressive paralysis and death, typically within 3-5 years. Although the heritability of ALS is about 60%, only about 11% is explained by common gene variants, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication and shorten naturally with age. Read More

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http://dx.doi.org/10.1080/21678421.2019.1586951DOI Listing
April 2019
4 Reads

Lack of consensus in ALS genetic testing practices and divergent views between ALS clinicians and patients.

Amyotroph Lateral Scler Frontotemporal Degener 2019 Apr 1:1-6. Epub 2019 Apr 1.

a Division of Human Genetics , The Ohio State University Medical Center , Columbus , OH , USA.

Recent advances in ALS gene discovery have both empowered and challenged clinicians providing evaluation and care for persons with ALS, many of whom seek an answer as to the cause of their condition. In order to study clinician practices and attitudes towards genetic testing, we surveyed members of the Northeast ALS Consortium, an international group of specialist ALS clinicians; responses were received from 80 of 255 (response rate = 31.4%). Read More

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http://dx.doi.org/10.1080/21678421.2019.1582670DOI Listing
April 2019
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Brain Connectivity and Information-Flow Breakdown Revealed by a Minimum Spanning Tree-Based Analysis of MRI Data in Behavioral Variant Frontotemporal Dementia.

Front Neurosci 2019 14;13:211. Epub 2019 Mar 14.

Medical and Genomic Statistics Unit, Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.

Brain functional disruption and cognitive shortfalls as consequences of neurodegeneration are among the most investigated aspects in current clinical research. Traditionally, specific anatomical and behavioral traits have been associated with neurodegeneration, thus directly translatable in clinical terms. However, these qualitative traits, do not account for the extensive information flow breakdown within the functional brain network that deeply affect cognitive skills. Read More

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http://dx.doi.org/10.3389/fnins.2019.00211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427927PMC
March 2019
1 Read

Fractionating the Rey Auditory Verbal Learning Test: Distinct roles of large-scale cortical networks in prodromal Alzheimer's disease.

Neuropsychologia 2019 Mar 28;129:83-92. Epub 2019 Mar 28.

Department of Neurology, Frontotemporal Disorders Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Successful episodic memory calls upon a number of different cognitive processes that are supported by the coordination of several large-scale cortical networks. Previous work from our group has demonstrated dissociable anatomic substrates at different stages of memory in patients with dementia due to Alzheimer's disease (AD). The aim of the current study was to extend the understanding of brain-behavior associations underlying a commonly administered neuropsychological assessment of verbal episodic memory (Rey Auditory Verbal Learning Test; RAVLT) by determining the cortical network contributions to the performance at early vs. Read More

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http://dx.doi.org/10.1016/j.neuropsychologia.2019.03.015DOI Listing
March 2019
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Major depressive disorder masking frontotemporal dementia secondary to C9orf72 mutation: A case report.

Rev Neurol (Paris) 2019 Mar 28. Epub 2019 Mar 28.

Department of neurology and neuropsychology La Timone university hospital, 13005 Marseille, France; UMR 7249, CNRS, école Centrale Marseille, institut Fresnel, Aix-Marseille université, Marseille, France.

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http://dx.doi.org/10.1016/j.neurol.2018.09.019DOI Listing
March 2019
6 Reads

Frontotemporal Dementia: A Clinical Review.

Semin Neurol 2019 04 29;39(2):251-263. Epub 2019 Mar 29.

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.

Frontotemporal dementias are a clinically, neuroanatomically, and pathologically diverse group of diseases that collectively constitute an important cause of young-onset dementia. Clinically, frontotemporal dementias characteristically strike capacities that define us as individuals, presenting broadly as disorders of social behavior or language. Neurobiologically, these diseases can be regarded as "molecular nexopathies," a paradigm for selective targeting and destruction of brain networks by pathogenic proteins. Read More

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http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1683379
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http://dx.doi.org/10.1055/s-0039-1683379DOI Listing
April 2019
2 Reads

Alzheimer's Disease Including Focal Presentations.

Semin Neurol 2019 Apr 29;39(2):213-226. Epub 2019 Mar 29.

Department of Neurology, Institute of Memory and Alzheimer's Disease, Assistance Publique - Hopitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.

Alzheimer's disease (AD) is the commonest neurodegenerative disease and the most frequent cause of dementia. It affects 30 million people worldwide. Current research criteria focus on biomarkers' status for amyloid and tau using positron emission tomography and cerebrospinal fluid analysis, independent of clinical status. Read More

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http://dx.doi.org/10.1055/s-0039-1681041DOI Listing
April 2019
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Neuroimaging in Dementias.

Semin Neurol 2019 Apr 29;39(2):188-199. Epub 2019 Mar 29.

Department of Radiology of Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.

Dementia is a global health issue, the burden of which will worsen with an increasingly aging population. Alzheimer's disease (AD) is the most common dementia, with 50 to 60% of all dementias attributable to AD alone, while the rest are mostly due to frontotemporal lobar dementia, dementia with Lewy bodies, Parkinson's disease dementia, and vascular dementia. Diagnosis of dementias is made clinically with the aid of other testing modalities including neuroimaging. Read More

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http://dx.doi.org/10.1055/s-0039-1678580DOI Listing
April 2019
1 Read