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Dementia frontotemporal

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https://www.readbyqxmd.com/read/28101324/oxytocin-for-frontotemporal-dementia-a-systematic-review
#1
REVIEW
Rajesh R Tampi, Michael Maksimowski, Mohsina Ahmed, Deena J Tampi
BACKGROUND: The aim of this systematic review is to identify published randomized controlled trials (RCTs) that evaluated the use of oxytocin in individuals with frontotemporal dementia (FTD). METHODS: A literature search was conducted of PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration databases for RCTs in any language that evaluated the use of oxytocin in individuals with FTD. Bibliographic databases of published articles were also searched for additional studies...
January 2017: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/28100023/frontotemporal-lobar-degeneration-pathogenesis-pathology-and-pathways-to-phenotype
#2
REVIEW
David Ma Mann, Julie S Snowden
Frontotemporal Lobar Degeneration (FTLD) is a clinically, pathologically and genetically heterogeneous group of disorders that affect principally the frontal and temporal lobes of the brain. There are three major associated clinical syndromes, behavioural variant frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA); three principal histologies, involving tau, TDP-43 and FUS proteins; and mutations in three major genes, MAPT, GRN and C9orf72, along with several other less common gene mutations...
January 18, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28097206/-18-f-av-1451-pet-in-behavioral-variant-frontotemporal-dementia-due-to-mapt-mutation
#3
W Richard Bevan Jones, Thomas E Cope, Luca Passamonti, Tim D Fryer, Young T Hong, Franklin Aigbirhio, Jillian J Kril, Shelley L Forrest, Kieren Allinson, Jonathan P Coles, P Simon Jones, Maria G Spillantini, John R Hodges, John T O'Brien, James B Rowe
The validation of tau radioligands could improve the diagnosis of frontotemporal lobar degeneration and the assessment of disease-modifying therapies. Here, we demonstrate that binding of the tau radioligand [(18)F]AV-1451 was significantly abnormal in both magnitude and distribution in a patient with familial frontotemporal dementia due to a MAPT 10 + 16C>T gene mutation, recapitulating the pattern of neuropathology seen in her father. Given the genetic diagnosis and the non-Alzheimer's pathology, these findings suggest that [(18)F]AV-1451 might be a useful biomarker in primary tauopathies...
December 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28096243/fused-in-sarcoma-neuropathology-in-neurodegenerative-disease
#4
Ian R A Mackenzie, Manuela Neumann
Abnormal intracellular accumulation of the fused in sarcoma (FUS) protein is the characteristic pathological feature of cases of familial amyotrophic lateral sclerosis (ALS) caused by FUS mutations (ALS-FUS) and several uncommon disorders that may present with sporadic frontotemporal dementia (FTLD-FUS). Although these findings provide further support for the concept that ALS and FTD are closely related clinical syndromes with an overlapping molecular basis, important differences in the pathological features and results from experimental models indicate that ALS-FUS and FTLD-FUS have distinct pathogenic mechanisms...
January 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28093491/early-microgliosis-precedes-neuronal-loss-and-behavioural-impairment-in-mice-with-a-frontotemporal-dementia-causing-chmp2b-mutation
#5
Emma L Clayton, Renzo Mancuso, Troels Tolstrup Nielsen, Sarah Mizielinska, Holly Holmes, Nicholas Powell, Frances Norona, Jytte Overgaard Larsen, Carmelo Milioto, Katherine M Wilson, Mark F Lythgoe, Sebastian Ourselin, Jörgen E Nielsen, Peter Johannsen, Ida Holm, John Collinge, A Frej, Peter L Oliver, Diego Gomez-Nicola, Adrian M Isaacs
Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD...
January 16, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28091722/hyperphosphorylated-tau-causes-reduced-hippocampal-ca1-excitability-by-relocating-the-axon-initial-segment
#6
Robert John Hatch, Yan Wei, Di Xia, Jürgen Götz
Hyperphosphorylated tau has a critical role in tauopathies such as Alzheimer's disease and frontotemporal dementia, impairing neuronal function and eventually leading to neurodegeneration. A critical role for tau is supported by studies in transgenic mouse models that express the P301L tau mutation found in cases of familial frontotemporal dementia, with the accumulation of hyperphosphorylated tau in the hippocampus causing reductions in hippocampal long-term potentiation and impairments in spatial learning and memory...
January 16, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28088537/mouse-models-of-frontotemporal-dementia-a-comparison-of-phenotypes-with-clinical-symptomatology
#7
REVIEW
Rebekah M Ahmed, Muireann Irish, Janet van Eersel, Arne Ittner, Yazi D Ke, Alexander Volkerling, Julia van der Hoven, Kimi Tanaka, Tim Karl, Michael Kassiou, Jillian J Kril, Olivier Piguet, Jürgen Götz, Matthew C Kiernan, Glenda M Halliday, John R Hodges, Lars M Ittner
Frontotemporal dementia (FTD) is the second most common cause of young onset dementia. It is increasingly recognized that there is a clinical continuum between FTD and amyotrophic lateral sclerosis (ALS). At a clinical, pathological and genetic level there is much heterogeneity in FTD, meaning that our understanding of this condition, pathophysiology and development of treatments has been limited. A number of mouse models focusing predominantly on recapitulating neuropathological and molecular changes of disease have been developed, with most transgenic lines expressing a single specific protein or genetic mutation...
January 11, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28087828/tdp-43-pathology-and-memory-impairment-in-elders-without-pathologic-diagnoses-of-ad-or-ftld
#8
Sukriti Nag, Lei Yu, Robert S Wilson, Er-Yun Chen, David A Bennett, Julie A Schneider
OBJECTIVE: To investigate the association of TAR DNA-binding protein 43 (TDP-43) pathology with memory, other cognitive domains, and dementia in community-dwelling elders without pathologic diagnoses of Alzheimer disease (AD) or frontotemporal lobar degeneration (FTLD). METHODS: Of 1,058 autopsied participants, 343 (32.4%) did not have pathologic diagnoses of AD or FTLD. Diagnosis of dementia was based on clinical evaluation and cognitive performance tests, which were used to create summary measures of global cognition and of 5 cognitive domains...
January 13, 2017: Neurology
https://www.readbyqxmd.com/read/28087719/genetics-insight-into-the-amyotrophic-lateral-sclerosis-frontotemporal-dementia-spectrum
#9
REVIEW
Ai-Ling Ji, Xia Zhang, Wei-Wei Chen, Wen-Juan Huang
Recent genetic discoveries have dramatically changed our understanding of two major neurodegenerative conditions. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are common, devastating diseases of the brain. For decades, ALS and FTD were classified as movement and cognitive disorders, respectively, due to their distinct clinical phenotypes. The recent identification of chromosome 9 open reading frame 72 (C9orf72) as the major gene causative of familial forms of ALS and FTD uncovered a new reality of a continuous FTD/ALS spectrum...
January 13, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28077166/threonine-175-a-novel-pathological-phosphorylation-site-on-tau-protein-linked-to-multiple-tauopathies
#10
Alexander J Moszczynski, Wencheng Yang, Robert Hammond, Lee Cyn Ang, Michael J Strong
Microtubule associated protein tau (tau) deposition is associated with a spectrum of neurodegenerative diseases collectively termed tauopathies. We have previously shown that amyotrophic lateral sclerosis (ALS) with cognitive impairment (ALSci) is associated with tau phosphorylation at Thr(175) and that this leads to activation of GSK3β which then induces phosphorylation at tau Thr(231). This latter step leads to dissociation of tau from microtubules and pathological tau fibril formation. To determine the extent to which this pathway is unique to ALS, we have investigated the expression of pThr(175) tau and pThr(231) tau across a range of frontotemporal degenerations...
January 11, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28072380/network-functional-connectivity-and-whole-brain-functional-connectomics-to-investigate-cognitive-decline-in-neurodegenerative-conditions
#11
REVIEW
O Dipasquale, Mara Cercignani
Non-invasive mapping of brain functional connectivity (FC) has played a fundamental role in neuroscience, and numerous scientists have been fascinated by its ability to reveal the brain's intricate morphology and functional properties. In recent years, two different techniques have been developed that are able to explore FC in pathophysiological conditions and to provide simple and non-invasive biomarkers for the detection of disease onset, severity and progression. These techniques are independent component analysis, which allows a network-based functional exploration of the brain, and graph theory, which provides a quantitative characterization of the whole-brain FC...
October 2016: Functional Neurology
https://www.readbyqxmd.com/read/28069809/the-receptor-interacting-serine-threonine-protein-kinase-1-ripk1-regulates-progranulin-levels
#12
Amanda R Mason, Lisa P Elia, Steven Finkbeiner
Progranulin (PGRN), a secreted growth factor, is a key regulator of inflammation and is genetically linked to two common and devastating neurodegenerative diseases. Haploinsufficiency mutations in GRN, the gene encoding PGRN, cause frontotemporal dementia (FTD) and a GRN SNP confers significantly increased risk for Alzheimer's disease (AD). Because cellular and animal data indicate that increasing PGRN can reverse phenotypes of both FTD and AD, modulating PGRN level has been proposed as a therapeutic strategy for both diseases...
January 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28069311/investigating-the-role-of-als-genes-chchd10-and-tuba4a-in-belgian-ftd-als-spectrum-patients
#13
Federica Perrone, Hung Phuoc Nguyen, Sara Van Mossevelde, Matthieu Moisse, Anne Sieben, Patrick Santens, Jan De Bleecker, Mathieu Vandenbulcke, Sebastiaan Engelborghs, Jonathan Baets, Patrick Cras, Rik Vandenberghe, Peter De Jonghe, Peter P De Deyn, Jean-Jacques Martin, Philip Van Damme, Christine Van Broeckhoven, Julie van der Zee
Mutation screening and phenotypic profiling of 2 amyotrophic lateral sclerosis-(ALS) and frontotemporal dementia-(FTD) associated genes, CHCHD10 and TUBA4A, were performed in a Belgian cohort of 459 FTD, 28 FTD-ALS, and 429 ALS patients. In CHCHD10, we identified a novel nonsense mutation (p.Gln108*) in a patient with atypical clinical FTD and pathology-confirmed Parkinson's disease (1/459, 0.22%) leading to loss of transcript. We further observed 3 previously described missense variants (p.Pro34Ser, p.Pro80Leu, and p...
December 21, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28067298/widespread-temporo-occipital-lobe-dysfunction-in-amyotrophic-lateral-sclerosis
#14
Kristian Loewe, Judith Machts, Jörn Kaufmann, Susanne Petri, Hans-Jochen Heinze, Christian Borgelt, Joseph Allen Harris, Stefan Vielhaber, Mircea Ariel Schoenfeld
Recent studies suggest that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) lie on a single clinical continuum. However, previous neuroimaging studies have found only limited involvement of temporal lobe regions in ALS. To better delineate possible temporal lobe involvement in ALS, the present study aimed to examine changes in functional connectivity across the whole brain, particularly with regard to extra-motor regions, in a group of 64 non-demented ALS patients and 38 healthy controls...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28064175/neuroimaging-of-inflammation-in-memory-and-related-other-disorders-nimrod-study-protocol-a-deep-phenotyping-cohort-study-of-the-role-of-brain-inflammation-in-dementia-depression-and-other-neurological-illnesses
#15
W Richard Bevan-Jones, Ajenthan Surendranathan, Luca Passamonti, Patricia Vázquez Rodríguez, Robert Arnold, Elijah Mak, Li Su, Jonathan P Coles, Tim D Fryer, Young T Hong, Guy Williams, Franklin Aigbirhio, James B Rowe, John T O'Brien
INTRODUCTION: Inflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such inflammation relates to other aspects of neuropathology, structural and functional changes in the brain and symptoms (as assessed via clinical and neuropsychological assessment and MRI). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows in vivo imaging of inflammation, amyloid and τ deposition, together with neuropsychological profiling, MRI and peripheral biomarker analysis...
January 7, 2017: BMJ Open
https://www.readbyqxmd.com/read/28062563/pathology-of-neurodegenerative-diseases
#16
Brittany N Dugger, Dennis W Dickson
Neurodegenerative disorders are characterized by progressive loss of selectively vulnerable populations of neurons, which contrasts with select static neuronal loss because of metabolic or toxic disorders. Neurodegenerative diseases can be classified according to primary clinical features (e.g., dementia, parkinsonism, or motor neuron disease), anatomic distribution of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), or principal molecular abnormality...
January 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28062558/biological-spectrum-of-amyotrophic-lateral-sclerosis-prions
#17
Magdalini Polymenidou, Don W Cleveland
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD) are two neurodegenerative diseases with distinct clinical features but common genetic causes and neuropathological signatures. Ten years after the RNA-binding protein TDP-43 was discovered as the main protein in the cytoplasmic inclusions that characterize ALS and FTLD, their pathogenic mechanisms have never seemed more complex. Indeed, discoveries of the past decade have revolutionized our understanding of these diseases, highlighting their genetic heterogeneity and the involvement of protein-RNA assemblies in their pathogenesis...
January 6, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28062555/antibody-therapeutics-targeting-a%C3%AE-and-tau
#18
Gilbert Gallardo, David M Holtzman
The astonishing findings that active and passive immunization against amyloid-β (Aβ) in mouse models of Alzheimer's disease (AD) dramatically decreased amyloid burden led to a rapid initiation of human clinical trials with much enthusiasm. However, methodological issues and adverse effects relating to these clinical trials arose, challenging the effectiveness and safety of these reagents. Efforts are now underway to develop safer immunotherapeutic approaches toward Aβ and the treatment of individuals at risk for AD before or in the earliest stages of cognitive decline with new hopes...
January 6, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28061383/increased-blood-brain-barrier-permeability-is-associated-with-dementia-and-diabetes-but-not-amyloid-pathology-or-apoe-genotype
#19
Shorena Janelidze, Joakim Hertze, Katarina Nägga, Karin Nilsson, Christer Nilsson, Malin Wennström, Danielle van Westen, Kaj Blennow, Henrik Zetterberg, Oskar Hansson
Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls...
December 5, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28060021/a-fresh-look-at-memory-loss-reexamining-frontotemporal-dementia
#20
Stephanie Zale, Lisa Dickerson
Frontotemporal dementia is a neurodegenerative disease affecting cognition and behavior in multiple devastating ways. This article highlights diagnostic features helpful in differentiating frontotemporal dementia from other dementias, most commonly Alzheimer disease.
February 2017: JAAPA: Official Journal of the American Academy of Physician Assistants
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