9,677 results match your criteria Frontotemporal Lobe Dementia

Frequency of frontotemporal dementia-related gene variants in Turkey.

Neurobiol Aging 2021 May 23. Epub 2021 May 23.

Department of Neurology, Istanbul University, Istanbul, Turkey.

Just as its clinical heterogeneity, genetic basis of Frontotemporal dementia (FTD) is also diverse and multiple molecular pathways are thought to be involved in disease pathogenesis. In the present study, FTD- related genes were evaluated in a Turkish cohort of 175 index FTD patients with a gene panel including GRN, MAPT, TARDBP, FUS, CHMP2B and VCP genes. Potential genetic associations were prospected in 16 patients (9. Read More

View Article and Full-Text PDF

Multiple pathways of toxicity induced by dipeptide repeat aggregates and GC RNA in a cellular model.

Elife 2021 Jun 23;10. Epub 2021 Jun 23.

Max Planck Institute of Biochemistry, Martinsried, Germany.

The most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia is a GC repeat expansion in the gene. This expansion gives rise to translation of aggregating dipeptide repeat (DPR) proteins, including poly-GA as the most abundant species. However, gain of toxic function effects have been attributed to either the DPRs or the pathological GC RNA. Read More

View Article and Full-Text PDF

Characterizing the Clinical Features and Atrophy Patterns of -Related Frontotemporal Dementia With Disease Progression Modeling.

Neurology 2021 Jun 22. Epub 2021 Jun 22.

Department of Neurology, Ludwig-Maximilians Universität München, Munich, Germany.

Background And Objective: Mutations in the gene cause frontotemporal dementia (FTD). Most previous studies investigating the neuroanatomical signature of mutations have grouped all different mutations together and shown an association with focal atrophy of the temporal lobe. However, the variability in atrophy patterns between each particular mutation is less well characterised. Read More

View Article and Full-Text PDF

Translation of the poly(GR) frame in C9ORF72-ALS/FTD is regulated by cis-elements involved in alternative splicing.

Neurobiol Aging 2021 May 8;105:327-332. Epub 2021 May 8.

Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address:

GGGGCC (GC) repeat expansion in the first intron of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia, two devastating age-dependent neurodegenerative disorders. Both sense and antisense repeat RNAs can be translated into 5 different dipeptide repeat proteins, such as poly(GR), which is toxic in various cellular and animal models. However, it remains unknown how poly(GR) is synthesized in patient neurons. Read More

View Article and Full-Text PDF

Neural mechanisms of psychosis vulnerability and perceptual abnormalities in the ALS-FTD spectrum.

Ann Clin Transl Neurol 2021 Jun 22. Epub 2021 Jun 22.

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

Objective: The aims of this study were to (i) explore psychotic experiences across the entire amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) spectrum from a clinical and genetic perspective, (ii) determine the rate of abnormal perceptual experiences across the five sensory modalities and (iii) explore the neurobiological factors that lead to psychosis vulnerability in ALS-FTD.

Methods: In a prospective case-controlled study design, 100 participants were enrolled including ALS (n = 37, 24% satisfied criteria for ALS-Plus), ALS-FTD (n = 11), bvFTD (n = 27) and healthy controls (n = 25). Psychotic experiences, perceptual abnormalities and psychosocial factors were determined by means of the clinical interview and carer and patient reports. Read More

View Article and Full-Text PDF

Discovery of quinuclidine modulators of cellular progranulin.

Bioorg Med Chem Lett 2021 Jun 18:128209. Epub 2021 Jun 18.

Arkuda Therapeutics, 200 Arsenal Yards Blvd Suite 220, Watertown, MA 02472, USA.

Phenotypic screening of an annotated small molecule library identified the quinuclidine tetrahydroisoquinoline solifenacin (1) as a robust enhancer of progranulin secretion with single digit micromolar potency in a murine microglial (BV-2) cell line. Subsequent SAR development led to the identification of 29 with a 38-fold decrease in muscarinic receptor antagonist activity and a 10-fold improvement in BV-2 potency. Read More

View Article and Full-Text PDF

Association Between Globular Glial Tauopathies and Frontotemporal Dementia-Expanding the Spectrum of Gliocentric Disorders: A Review.

JAMA Neurol 2021 Jun 21. Epub 2021 Jun 21.

Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada.

Importance: Globular glial tauopathies (GGTs), as defined by a consensus study in 2013, belong to the group of frontotemporal lobar degenerations and expand the spectrum of glial-predominant neurodegenerative diseases. Three neuropathological subtypes of GGT (types I-III) are characterized by phosphorylated tau-immunopositive inclusions that are predominantly in oligodendroglia and/or astroglia in the frontal, temporal, and/or precentral cortices. Type II is largely restricted to the corticospinal system. Read More

View Article and Full-Text PDF

Cardiac troponin T is elevated and increases longitudinally in ALS patients.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Jun 21:1-8. Epub 2021 Jun 21.

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

To test whether high-sensitivity cardiac troponin T (hs-cTnT) could act as a diagnostic or prognostic biomarker in ALS, comparing hs-cTnT to neurofilament light (NfL). We performed a case-control study, including 150 ALS patients, 28 ALS mimics, and 108 healthy controls, and a follow-up study of the ALS patients, during 2014-2020 in Stockholm, Sweden. We compared concentrations of hs-cTnT in plasma and NfL in the cerebrospinal fluid between cases and controls. Read More

View Article and Full-Text PDF

Altered ribosomal function and protein synthesis caused by tau.

Acta Neuropathol Commun 2021 Jun 19;9(1):110. Epub 2021 Jun 19.

Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia.

The synthesis of new proteins is a fundamental aspect of cellular life and is required for many neurological processes, including the formation, updating and extinction of long-term memories. Protein synthesis is impaired in neurodegenerative diseases including tauopathies, in which pathology is caused by aberrant changes to the microtubule-associated protein tau. We recently showed that both global de novo protein synthesis and the synthesis of select ribosomal proteins (RPs) are decreased in mouse models of frontotemporal dementia (FTD) which express mutant forms of tau. Read More

View Article and Full-Text PDF

Chemical and genetic rescue of in vivo progranulin-deficient lysosomal and autophagic defects.

Proc Natl Acad Sci U S A 2021 Jun;118(25)

Centre de Recherche du Centre Hospitalier de l'Université de Montreal, Université de Montréal, Montréal, QC, Canada H2X 3H8;

In 2006, mutations were first linked to frontotemporal dementia (FTD), the leading cause of non-Alzheimer dementias. While much research has been dedicated to understanding the genetic causes of the disease, our understanding of the mechanistic impacts of deficiency has only recently begun to take shape. With no known cure or treatment available for -related FTD, there is a growing need to rapidly advance genetic and/or small-molecule therapeutics for this disease. Read More

View Article and Full-Text PDF

Highlighting the clinical potential of HTT repeat expansions in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

Neuron 2021 Jun;109(12):1947-1948

Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD 21287, USA; Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK. Electronic address:

View Article and Full-Text PDF

MRI-guided histology of TDP-43 knock-in mice implicates parvalbumin interneuron loss, impaired neurogenesis and aberrant neurodevelopment in amyotrophic lateral sclerosis-frontotemporal dementia.

Brain Commun 2021 27;3(2):fcab114. Epub 2021 May 27.

Department of Basic and Clinical Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London SE5 9RT, UK.

Amyotrophic lateral sclerosis and frontotemporal dementia are overlapping diseases in which MRI reveals brain structural changes in advance of symptom onset. Recapitulating these changes in preclinical models would help to improve our understanding of the molecular causes underlying regionally selective brain atrophy in early disease. We therefore investigated the translational potential of the TDP-43 knock-in mouse model of amyotrophic lateral sclerosis-frontotemporal dementia using MRI. Read More

View Article and Full-Text PDF

C9orf72 deficiency promotes microglial-mediated synaptic loss in aging and amyloid accumulation.

Neuron 2021 Jun 5. Epub 2021 Jun 5.

Center for Neural Science and Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Department of Neurology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. Electronic address:

C9orf72 repeat expansions cause inherited amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) and result in both loss of C9orf72 protein expression and production of potentially toxic RNA and dipeptide repeat proteins. In addition to ALS/FTD, C9orf72 repeat expansions have been reported in a broad array of neurodegenerative syndromes, including Alzheimer's disease. Here we show that C9orf72 deficiency promotes a change in the homeostatic signature in microglia and a transition to an inflammatory state characterized by an enhanced type I IFN signature. Read More

View Article and Full-Text PDF

An autopsy case of corticobasal syndrome with pure diffuse Lewy Body Disease.

Neurocase 2021 Jun 15:1-7. Epub 2021 Jun 15.

Department of Neurology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.

Corticobasal syndrome (CBS) is associated with diverse pathological substrates such as tau, prion protein, transactive response and, rarely, alpha synuclein. We report the case of a54-year-old man, who presented with asymmetric levodopa-poor-responsive parkinsonism, frontal lobe signs and behavioral changes. He was diagnosed with CBS, and postmortem analyses revealed Lewy body disease Braak stage VI without comorbid pathologies. Read More

View Article and Full-Text PDF

Genome-wide CRISPR screen identifies protein pathways modulating tau protein levels in neurons.

Commun Biol 2021 Jun 14;4(1):736. Epub 2021 Jun 14.

Department of Neuroscience, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.

Aggregates of hyperphosphorylated tau protein are a pathological hallmark of more than 20 distinct neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, and frontotemporal dementia. While the exact mechanism of tau aggregation is unknown, the accumulation of aggregates correlates with disease progression. Here we report a genome-wide CRISPR screen to identify modulators of endogenous tau protein for the first time. Read More

View Article and Full-Text PDF

A Multiparametric MRI Protocol for Evaluation of Cognitive Insufficiency, Dementia and Traumatic Brain Injury (TBI): A Case Series.

CNS Spectr 2021 Apr;26(2):179

Colorado Springs Neurological Associates, Colorado Springs, CO, USA.

Background: The purpose of this work was to determine the extent to which a multiparametric magnetic resonance imaging (MRI) approach to patients with dementia and/or traumatic brain injury (TBI) can help to determine the most likely diagnosis and the prognosis of these patients.

Objective: Volumetric brain MRI alone is recognized as a useful imaging tool to differentiate behavioral variant frontotemporal dementia (bvFTD) from the more common Alzheimer's disease (AD). Our objective is to create a protocol that will provide additional non-standard, objective imaging data that can be utilized clinically to distinguish common and uncommon forms of dementia and TBI. Read More

View Article and Full-Text PDF

Research on Emotion Recognition and Dementias: Foundations and Prospects.

J Alzheimers Dis 2021 Jun 7. Epub 2021 Jun 7.

Departamento de Psicología Evolutiva y de la Educación, Universitat de Valencia, Spain.

Background: The study of emotion recognition could be crucial for detecting alterations in certain cognitive areas or as an early sign of neurological disorders.

Objective: The main objective of the study is to characterize research development on emotion recognition, identifying the intellectual structure that supports this area of knowledge, and the main lines of research attracting investigators' interest.

Methods: We identified publications on emotion recognition and dementia included in the Web of Science Core Collection, analyzing the scientific output and main disciplines involved in generating knowledge in the area. Read More

View Article and Full-Text PDF

Family-based exome sequencing identifies RBM45 as a possible candidate gene for frontotemporal dementia and amyotrophic lateral sclerosis.

Neurobiol Dis 2021 Jun 9;156:105421. Epub 2021 Jun 9.

Neurodegenerative Brain Diseases, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Institute Born-Bunge, Antwerp, Belgium. Electronic address:

Neurodegenerative disorders like frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are pathologically characterized by toxic protein deposition in the cytoplasm or nucleus of affected neurons and glial cells. Many of these aggregated proteins belong to the class of RNA binding proteins (RBP), and, when mutated, account for a significant subset of familial ALS and FTD cases. Here, we present first genetic evidence for the RBP gene RBM45 in the FTD-ALS spectrum. Read More

View Article and Full-Text PDF

Long non-coding RNAs in neurodegenerative diseases.

Neurochem Int 2021 Jun 10;148:105096. Epub 2021 Jun 10.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Neurodegenerative diseases are gradually becoming the main burden of society. The morbidity and mortality caused by neurodegenerative diseases remain significant health-care concerns. For most neurodegenerative diseases, there are no effective treatments. Read More

View Article and Full-Text PDF

Adiabatic dynamic causal modelling.

Neuroimage 2021 Jun 8;238:118243. Epub 2021 Jun 8.

The Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, UK.

This technical note introduces adiabatic dynamic causal modelling, a method for inferring slow changes in biophysical parameters that control fluctuations of fast neuronal states. The application domain we have in mind is inferring slow changes in variables (e.g. Read More

View Article and Full-Text PDF

18F-THK5351 PET Can Identify Core Lesions in Different Amyotrophic Lateral Sclerosis Phenotypes.

Clin Nucl Med 2021 Jun 10. Epub 2021 Jun 10.

From the Department of Neurology, Tokyo Metropolitan Geriatric Hospital Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology Department of Diagnostic Radiology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.

Abstract: Two patients with different amyotrophic lateral sclerosis (ALS) phenotypes underwent 18F-THK5351 PET to visualize lesions undergoing astrogliosis by measuring monoamine oxidase B activity. Patient 1 was a 57-year-old man with flail leg syndrome. Elevated uptake was observed inside the motor cortex, corresponding to the leg area in a cortical homunculus. Read More

View Article and Full-Text PDF

TDP-43 stabilizes G3BP1 mRNA: relevance to amyotrophic lateral sclerosis/frontotemporal dementia.

Brain 2021 Jun 11. Epub 2021 Jun 11.

Department of Neurosciences, Université de Montréal, Montreal, QC, H3A 0E8, Canada.

TDP-43 nuclear depletion and concurrent cytoplasmic accumulation in vulnerable neurons is a hallmark feature of progressive neurodegenerative proteinopathies such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cellular stress signalling and stress granule dynamics are now recognized to play a role in ALS/FTD pathogenesis. Defective stress granule assembly is associated with increased cellular vulnerability and death. Read More

View Article and Full-Text PDF

Specific support needs and experiences of carers of people with frontotemporal dementia: A systematic review.

Dementia (London) 2021 Jun 11:14713012211022982. Epub 2021 Jun 11.

Department of Clinical, Educational and Health Psychology, University College London, London, UK; ADAPT Lab, UCL, London, UK.

Introduction: Frontotemporal dementia (FTD) is one of the most common types of dementia in persons younger than 65 years of age. Diagnosis is often delayed due to slow, gradual decline and misinterpretation of 'non-typical' dementia symptoms. Informal carers of people with FTD experience greater levels of overall burden than carers of people with other forms of dementia. Read More

View Article and Full-Text PDF

A disease-specific metabolic imaging marker for diagnosis and progression evaluation of semantic variant primary progressive aphasia.

Eur J Neurol 2021 Jun 10. Epub 2021 Jun 10.

PET Center, Huashan Hospital, Fudan University, Shanghai, China.

Background: The diagnosis and monitoring of semantic variant primary progressive aphasia (sv-PPA) are clinically challenging. We aimed to establish a distinctive metabolic pattern in sv-PPA for diagnosis and severity evaluation.

Methods: Fifteen sv-PPA patients and 15 controls were enrolled to identify sv-PPA-related pattern (sv-PPARP) by principal component analysis of F-fluorodeoxyglucose positron-emission-tomography. Read More

View Article and Full-Text PDF

Effects of Alzheimer's Disease-Related Proteins on the Chirality of Brain Endothelial Cells.

Cell Mol Bioeng 2021 Jun 22;14(3):231-240. Epub 2021 Mar 22.

Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180 USA.

Introduction: Cell chirality is an intrinsic cellular property that determines the directionality of cellular polarization along the left-right axis. We recently show that endothelial cell chirality can influence intercellular junction formation and alter trans-endothelial permeability, depending on the uniformity of the chirality of adjacent cells, which suggests a potential role for cell chirality in neurodegenerative diseases with blood-brain barrier (BBB) dysfunctions, such as Alzheimer's disease (AD). In this study, we determined the effects of AD-related proteins amyloid-β (Aβ), tau, and apolipoprotein E4 (ApoE4) on the chiral bias of the endothelial cell component in BBB. Read More

View Article and Full-Text PDF

Tracing Neurological Diseases in the Presymptomatic Phase: Insights From Neurofilament Light Chain.

Front Neurosci 2021 24;15:672954. Epub 2021 May 24.

Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

The identification of neurological diseases in their presymptomatic phase will be a fundamental aim in the coming years. This step is necessary both to optimize early diagnostics and to verify the effectiveness of experimental disease modifying drugs in the early stages of diseases. Among the biomarkers that can detect neurological diseases already in their preclinical phase, neurofilament light chain (NfL) has given the most promising results. Read More

View Article and Full-Text PDF

Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias.

J Neurol Neurosurg Psychiatry 2021 Jun 8. Epub 2021 Jun 8.

Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalunya, Spain.

Objectives: All categories included in the AT(N) classification can now be measured in plasma. However, their agreement with cerebrospinal fluid (CSF) markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis of patients with Alzheimer's disease (AD) through an easy and minimally invasive approach. Read More

View Article and Full-Text PDF

Proline/arginine dipeptide repeat polymers derail protein folding in amyotrophic lateral sclerosis.

Nat Commun 2021 06 7;12(1):3396. Epub 2021 Jun 7.

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

Amyotrophic lateral sclerosis and frontotemporal dementia are two neurodegenerative diseases with overlapping clinical features and the pathological hallmark of cytoplasmic deposits of misfolded proteins. The most frequent cause of familial forms of these diseases is a hexanucleotide repeat expansion in the non-coding region of the C9ORF72 gene that is translated into dipeptide repeat polymers. Here we show that proline/arginine repeat polymers derail protein folding by sequestering molecular chaperones. Read More

View Article and Full-Text PDF

A multicentre validation study of the diagnostic value of plasma neurofilament light.

Nat Commun 2021 06 7;12(1):3400. Epub 2021 Jun 7.

Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, QC, Canada.

Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. Read More

View Article and Full-Text PDF

Recognition of musical emotions in the behavioral variant of frontotemporal dementia.

Rev Colomb Psiquiatr (Engl Ed) 2021 Apr-Jun;50(2):74-81

Universidad Militar Nueva Granada, Bogotá, Colombia.

Introduction: Multiple investigations have revealed that patients with behavioral variant of frontotemporal dementia (bvFTD) experience difficulty recognizing emotional signals in multiple processing modalities (e.g., faces, prosody). Read More

View Article and Full-Text PDF
September 2019