Read by QxMD icon Read


Amrutha Swaminathan, Marilou Bouffard, Meijiang Liao, Sarah Ryan, Janis Bennion Callister, Stuart M Pickering-Brown, Gary Alan Barclay Armstrong, Pierre Drapeau
Large expansions of hexanucleotide GGGGCC (G4C2) repeats (hundreds to thousands) in the first intron of the chromosome 9 open reading frame 72 (C9orf72) locus are the strongest known genetic factor associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS/FTLD). Different hypotheses exist about the underlying disease mechanism including loss-of-function by haploinsufficiency, toxicity arising as a result of RNA or dipeptide repeats (DPRs). Five different DPRs are produced by repeat-associated non-ATG-initiated (RAN) translation of the G4C2 repeats...
March 8, 2018: Human Molecular Genetics
Lieke H H Meeter, Everard G Vijverberg, Marta Del Campo, Annemieke J M Rozemuller, Laura Donker Kaat, Frank Jan de Jong, Wiesje M van der Flier, Charlotte E Teunissen, John C van Swieten, Yolande A L Pijnenburg
OBJECTIVE: To examine the clinical value of neurofilament light chain (NfL) and the phospho-tau/total tau ratio (p/t-tau) across the entire frontotemporal dementia (FTD) spectrum in a large, well-defined cohort. METHODS: CSF NfL and p/t-tau levels were studied in 361 patients with FTD: 179 behavioral variant FTD, 17 FTD with motor neuron disease (FTD-MND), 36 semantic variant primary progressive aphasia (PPA), 19 nonfluent variant PPA, 4 logopenic variant PPA (lvPPA), 42 corticobasal syndrome, and 64 progressive supranuclear palsy...
March 7, 2018: Neurology
Alyssa Caplan, Gabe Marx, Jonathan Elofson, Claire Lis, Lea Grinberg, Bruce Miller, Howard Rosen
Neurodegenerative diseases are caused by aggregation of specific proteins that catalyze a cascade of changes that ultimately lead to neurodegeneration. This concept guides current diagnostic approaches, as well as clinical trials, that focus on detecting or removing amyloid or tau from the brain. The semantic variant of primary progressive aphasia (svPPA), a clinical syndrome associated with frontotemporal lobar degeneration (FTLD) pathology, is usually associated with the molecular pathology TDP-C, but there are cases with TDP-B and Pick's disease...
March 6, 2018: Neurocase
Ju Gao, Luwen Wang, Mikayla L Huntley, George Perry, Xinglong Wang
Neurodegeneration, a term that refers to the progressive loss of structure and function of neurons, is a feature of many neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). There is no cure or treatment available that can prevent or reverse neurodegenerative conditions. The causes of neurodegeneration in these diseases remain largely unknown, yet an extremely small proportion of these devastating diseases are associated with genetic mutations in proteins involved in a wide range of cellular pathways and processes...
February 27, 2018: Journal of Neurochemistry
Kasper Katisko, Annakaisa Haapasalo, Anne Koivisto, Johanna Krüger, Päivi Hartikainen, Ville Korhonen, Seppo Helisalmi, Sanna-Kaisa Herukka, Anne M Remes, Eino Solje
 Several studies have reported reduced risk of cancer in patients with Alzheimer's disease (AD) or Parkinson's disease. The relationship between cancer and frontotemporal lobar degeneration (FTLD) has not been previously reported. Here, our aim was to evaluate the occurrence of cancer in Finnish FTLD patients with a high proportion of C9ORF72 repeat expansion carriers in comparison to age- and sex-matched group of AD patients and control subjects classified as not cognitively impaired (NCI). The prevalence of cancer was 9...
2018: Journal of Alzheimer's Disease: JAD
Emily Feneberg, Elizabeth Gray, Olaf Ansorge, Kevin Talbot, Martin R Turner
TDP-43 accumulates in nerve cells of nearly all cases of amyotrophic lateral sclerosis (ALS; the commonest form of motor neuron disease) and in the majority of Tau-negative frontotemporal lobar degeneration (FTLD). There is currently no biochemical test or marker of disease activity for ALS or FTLD, and the clinical diagnosis depends on the opinion of an experienced neurologist. TDP-43 has a key role in the pathogenesis of ALS/FTLD. Measuring TDP-43 in easily accessible biofluids, such as blood or cerebrospinal fluid, might reduce diagnostic delay and offer a readout for use in future drug trials...
February 19, 2018: Molecular Neurobiology
Hongbo Chen, Mark W Kankel, Susan C Su, Steve W S Han, Dimitry Ofengeim
Although amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, was first described in 1874, a flurry of genetic discoveries in the last 10 years has markedly increased our understanding of this disease. These findings have not only enhanced our knowledge of mechanisms leading to ALS, but also have revealed that ALS shares many genetic causes with another neurodegenerative disease, frontotemporal lobar dementia (FTLD). In this review, we survey how recent genetic studies have bridged our mechanistic understanding of these two related diseases and how the genetics behind ALS and FTLD point to complex disorders, implicating non-neuronal cell types in disease pathophysiology...
February 19, 2018: Cell Death and Differentiation
Sang Won Seo, Marie-Pierre Thibodeau, David C Perry, Alice Hua, Manu Sidhu, Isabel Sible, Jose Norberto S Vargas, Stephanie E Gaus, Gil D Rabinovici, Katherine D Rankin, Adam L Boxer, Joel H Kramer, Howard J Rosen, Maria Luisa Gorno-Tempini, Lea T Grinberg, Eric J Huang, Stephen J DeArmond, John Q Trojanowski, Bruce L Miller, William W Seeley
OBJECTIVE: To examine clinicopathologic correlations in early vs late age at onset frontotemporal dementia (FTD) and frontotemporal lobar degeneration (FTLD). METHODS: All patients were clinically evaluated and prospectively diagnosed at the UCSF Memory and Aging Center. Two consecutive series were included: (1) patients with a clinically diagnosed FTD syndrome who underwent autopsy (cohort 1) and (2) patients with a primary pathologic diagnosis of FTLD, regardless of the clinical syndrome (cohort 2)...
February 16, 2018: Neurology
Thaís B Lima-Silva, Valéria S Bahia, Mário A Cecchini, Luciana Cassimiro, Henrique C Guimarães, Leandro B Gambogi, Paulo Caramelli, Márcio Balthazar, Benito Damasceno, Sônia M D Brucki, Leonardo C de Souza, Ricardo Nitrini, Eneida Mioshi, Mônica S Yassuda
INTRODUCTION: Few studies on instruments for staging frontotemporal dementia (FTD) have been conducted. OBJECTIVE: The objective of this study was to analyze the factor structure, internal consistency, reliability, and convergent validity of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS). METHODS: A total of 97 individuals aged 40 years and above with >2 years' education took part in the study, 31 patients diagnosed with behavioral variant FTD (bvFTD), 8 patients with primary progressive aphasia, 28 with Alzheimer disease, 8 with mild cognitive impairment, and a control group of 22 healthy subjects...
February 13, 2018: Alzheimer Disease and Associated Disorders
Yumi Takano, Keiko Kunitoki, Yasuko Tatewaki, Tatsushi Mutoh, Tomoko Totsune, Hideo Shimomura, Manabu Nakagawa, Hiroyuki Arai, Yasuyuki Taki
BACKGROUND Semantic dementia (SD) is a type of primary progressive aphasia with prominent language dysfunction, mostly within the spectrum of frontotemporal lobar degeneration (FTLD). Although there is an overlap in clinical manifestations of SD attributable to FTLD and neuropathologically proven Alzheimer disease (AD), clinical diagnostic clues are not readily available. We present a characteristic finding based on a single-photon emission computed tomography (SPECT)-based regional cerebral blood flow study and its statistical imaging analysis for a rare case of SD with AD-like pathology...
February 12, 2018: American Journal of Case Reports
Yinan Nan, Shaoqing Wang, William Jia
Transactive response DNA-binding protein 43kD (TDP-43) is a major component of tau-negative and ubiquitin-positive inclusions that characterize ALS (amyotrophic lateral sclerosis) and FTLD (frontotemporal lobar degeneration). Due to its central role in neurodegenerative disease pathogenesis, most research recently has focused on its role associated with neurodegeneration disease, research on neuron and glial cell showed that pathological TDP-43 is associated with cell apoptosis which lead to loss of functional neurons and glial cells...
February 5, 2018: Biochemical and Biophysical Research Communications
Garrett S Gibbons, Rachel A Banks, Bumjin Kim, Lakshmi Changolkar, Dawn M Riddle, Susan N Leight, David J Irwin, John Q Trojanowski, Virginia M Y Lee
Aggregation of tau into fibrillar structures within the CNS is a pathological hallmark of a clinically heterogeneous set of neurodegenerative diseases termed tauopathies. Unique misfolded conformations of tau, referred to as strains, are hypothesized to underlie the distinct neuroanatomical and cellular distribution of pathological tau aggregates. Here, we report the identification of novel tau monoclonal antibodies (mAbs) that selectively bind to an Alzheimer disease (AD)-specific conformation of pathological tau...
February 5, 2018: Journal of Neuropathology and Experimental Neurology
Laura M Taylor, Pamela J McMillan, Nicole F Liachko, Timothy J Strovas, Bernardino Ghetti, Thomas D Bird, C Dirk Keene, Brian C Kraemer
BACKGROUND: Progressive neuron loss in the frontal and temporal lobes of the cerebral cortex typifies frontotemporal lobar degeneration (FTLD). FTLD sub types are classified on the basis of neuronal aggregated protein deposits, typically containing either aberrantly phosphorylated TDP-43 or tau. Our recent work demonstrated that tau tubulin kinases 1 and 2 (TTBK1/2) robustly phosphorylate TDP-43 and co-localize with phosphorylated TDP-43 in human postmortem neurons from FTLD patients...
February 6, 2018: Molecular Neurodegeneration
Kyota Fujita, Xigui Chen, Hidenori Homma, Kazuhiko Tagawa, Mutsuki Amano, Ayumu Saito, Seiya Imoto, Hiroyasu Akatsu, Yoshio Hashizume, Kozo Kaibuchi, Satoru Miyano, Hitoshi Okazawa
Mutations in the progranulin (PGRN) gene cause a tau pathology-negative and TDP43 pathology-positive form of frontotemporal lobar degeneration (FTLD-TDP). We generated a knock-in mouse harboring the R504X mutation (PGRN-KI). Phosphoproteomic analysis of this model revealed activation of signaling pathways connecting PKC and MAPK to tau prior to TDP43 aggregation and cognitive impairments, and identified PKCα as the kinase responsible for the early-stage tau phosphorylation at Ser203. Disinhibition of Gas6 binding to Tyro3 due to PGRN reduction results in activation of PKCα via PLCγ, inducing tau phosphorylation at Ser203, mislocalization of tau to dendritic spines, and spine loss...
January 30, 2018: Nature Communications
Claudia Saraceno, Marcella Catania, Anna Paterlini, Silvia Fostinelli, Miriam Ciani, Roberta Zanardini, Giuliano Binetti, Giuseppe Di Fede, Paola Caroppo, Luisa Benussi, Roberta Ghidoni, Silvia Bolognin
The term frontotemporal lobar degeneration (FTLD) defines a group of heterogeneous conditions histologically characterized by neuronal degeneration, inclusions of various proteins, and synaptic loss. However, the molecular mechanisms contributing to these alterations are still unknown. As the Rho-GTPase family member Cell division cycle 42 (Cdc42) plays a key role in the regulation of actin cytoskeleton dynamics and spine formation, we investigated whether Cdc42 protein levels were altered in the disease. Cdc42 was increased in the frontal cortex of FTLD patients compared to age-matched controls, but also in Alzheimer's disease (AD) patients included in the data-set...
2018: Journal of Alzheimer's Disease: JAD
Anne Sieben, Sara Van Mossevelde, Eline Wauters, Sebastiaan Engelborghs, Julie van der Zee, Tim Van Langenhove, Patrick Santens, Marleen Praet, Paul Boon, Marijke Miatton, Sofie Van Hoecke, Mathieu Vandenbulcke, Rik Vandenberghe, Patrick Cras, Marc Cruts, Peter Paul De Deyn, Christine Van Broeckhoven, Jean-Jacques Martin
BACKGROUND: In this paper, we describe the clinical and neuropathological findings of nine members of the Belgian progranulin gene (GRN) founder family. In this family, the loss-of-function mutation IVS1 + 5G > C was identified in 2006. In 2007, a clinical description of the mutation carriers was published that revealed the clinical heterogeneity among IVS1 + 5G > C carriers. We report our comparison of our data with the published clinical and neuropathological characteristics of other GRN mutations as well as other frontotemporal lobar degeneration (FTLD) syndromes, and we present a review of the literature...
January 22, 2018: Alzheimer's Research & Therapy
Samir Abu-Rumeileh, Sabina Capellari, Michelangelo Stanzani-Maserati, Barbara Polischi, Paolo Martinelli, Paola Caroppo, Anna Ladogana, Piero Parchi
BACKGROUND: Neurofilament light chain protein (NfL) is a surrogate biomarker of neurodegeneration that has never been systematically tested, either alone or in combination with other biomarkers, in atypical/rapidly progressive neurodegenerative dementias (NDs). METHODS: Using validated, commercially available enzyme-linked immunosorbent assay kits, we measured cerebrospinal fluid (CSF) NfL, total tau (t-tau), phosphorylated tau, and β-amyloid 42 in subjects with a neuropathological or clinical diagnosis of prion disease (n = 141), Alzheimer's disease (AD) (n = 73), dementia with Lewy bodies (DLB) (n = 35), or frontotemporal lobar degeneration (FTLD) (n = 44)...
January 11, 2018: Alzheimer's Research & Therapy
Wen-Hua Su, Zhi-Hong Shi, Shu-Ling Liu, Xiao-Dan Wang, Shuai Liu, Yong Ji
Polymorphisms of the triggering receptor expressed on myeloid cells 2 (TREM2) gene have been reported to be potentially associated with the risks of developing frontotemporal lobar degeneration (FTLD), with inconsistent conclusions. This study aims to comprehensively investigate the potential role of TREM2 variants in FTLD risks via a meta-analysis. We included a total of eight eligible articles. For TREM2 rs75932628, we observed a significantly increased FTLD risk in the models of T vs. C [Association Test, odds ratio (OR) = 2...
January 10, 2018: Annals of Human Genetics
Julbert Caneus, Antoneta Granic, Rosa Rademakers, Dennis W Dickson, Christina M Coughlan, Heidi J Chial, Huntington Potter
Mutant Tau (MAPT) can lead to frontotemporal lobar degeneration (FTLD). Previous studies associated MAPT mutations and altered function with aneuploidy and chromosome instability in human lymphocytes and in Drosophila development. Here, we examine whether FTLD-causing mutations in human MAPT induce aneuploidy and apoptosis in the mammalian brain. First, aneuploidy was found in brain cells from MAPT mutant transgenic mice expressing FTLD mutant human MAPT. Then, brain neurons from mice homozygous or heterozygous for the Tau (Mapt) null allele were found to exhibit increasing levels of aneuploidy with decreasing Tau gene dosage...
December 27, 2017: Molecular Biology of the Cell
Salinee Jantrapirom, Luca Lo Piccolo, Hideki Yoshida, Masamitsu Yamaguchi
Ubiquilin (UBQLN) plays a crucial role in cellular proteostasis through its involvement in the ubiquitin proteasome system and autophagy. Mutations in the UBQLN2 gene have been implicated in amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal lobar dementia (ALS/FTLD). Previous studies reported a key role for UBQLN in Alzheimer's disease (AD); however, the mechanistic involvement of UBQLN in other neurodegenerative diseases remains unclear. The genome of Drosophila contains a single UBQLN homolog (dUbqn) that shows high similarity to UBQLN1 and UBQLN2; therefore, the fly is a useful model for characterizing the role of UBQLN in vivo in neurological disorders affecting locomotion and learning abilities...
December 13, 2017: Experimental Cell Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"