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Cerebral perfusion changes in presymptomatic genetic frontotemporal dementia
Henri JMM Mutsaerts, Saira S Mirza, Jan Petr, David L Thomas, David M Cash, Martina Bocchetta, Enrico De Vita, Arron WS Metcalfe, Zahra Shirzadi, Andrew D Robertson, Maria Carmela Tartaglia, Sara B Mitchell, Sandra E Black, Morris Freedman, David Tang-Wai, Ron Keren, Ekaterina Rogaeva, John van Swieten, Robert Laforce, Fabrizio Tagliavini, Barbara Borroni, Daniela Galimberti, James B Rowe, Caroline Graff, Giovanni B Frisoni, Elizabeth Finger, Sandro Sorbi, Alexandre de Mendonça, Jonathan D Rohrer, Bradley J MacIntosh, Mario Masellis, Genetic Frontotemporal dementia Initiative (GENFI)
Mar 25, 2019
Genetic forms of frontotemporal dementia are most commonly due to mutations in three genes, C9orf72, GRN or MAPT, with presymptomatic carriers from families representing those at risk. While cerebral blood flow shows differences...
arterial spin labelling cerebral blood flow genetic frontotemporal dementia presymptomatic biomarker Adult Aged Brain C9orf72 Protein Cerebrovascular Circulation Cross-Sectional Studies Female frontotemporal dementia Heterozygote Humans Magnetic Resonance Imaging Male Middle Aged Mutation Neuropsychological Tests Progranulins tau Proteins
Measurement of Tau Filament Fragmentation Provides Insights into Prion-like Spreading.
Franziska Kundel, Liu Hong, Benjamin Falcon, William A McEwan, Thomas CT Michaels, Georg Meisl, Noemi Esteras, Andrey Y Abramov, Tuomas JP Knowles, Michel Goedert, David Klenerman
Jul 13, 2018
The ordered assembly of amyloidogenic proteins causes a wide spectrum of common neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. These diseases share common features with prion diseases, in which...
Tau pathology in early Alzheimer's disease is linked to selective disruptions in neurophysiological network dynamics.
Ece Kocagoncu, Andrew Quinn, Azadeh Firouzian, Elisa Cooper, Andrea Greve, Roger Gunn, Gary Green, Mark W Woolrich, Richard N Henson, Simon Lovestone, Deep and Frequent Phenotyping study team, James B Rowe
Mar 12, 2020
Understanding the role of Tau protein aggregation in the pathogenesis of Alzheimer's disease is critical for the development of new Tau-based therapeutic strategies to slow or prevent dementia. We tested the hypothesis that Tau...
Alzheimer's Disease Connectivity Graph theory MEG PET Tau Aged Aged 80 and over Alzheimer Disease Cognition Female Humans Magnetoencephalography Male Middle Aged Molecular Imaging Occipital Lobe Parietal Lobe Positron-Emission Tomography protein aggregation Pathological Synaptic Transmission tau Proteins
Early symptoms in symptomatic and preclinical genetic frontotemporal lobar degeneration.
Tamara Paulo Tavares, Derek GV Mitchell, Kristy Kl Coleman, Brenda L Coleman, Christen L Shoesmith, Christopher R Butler, Isabel Santana, Adrian Danek, Alexander Gerhard, Alexandre de Mendonca, Barbara Borroni, Maria Carmela Tartaglia, Caroline Graff, Daniela Galimberti, Fabrizio Tagliavini, Fermin Moreno, Giovanni Frisoni, James Benedict Rowe, Johannes Levin, John Cornelis van Swieten, Markus Otto, Matthis Synofzik, Raquel Sanchez-Valle, Rik Vandenberghe, Robert Jr Laforce, Roberta Ghidoni, Sandro Sorbi, Simon Ducharme, Mario Masellis, Jonathan Rohrer, Elizabeth Finger, GENFI Initiative
May 07, 2020
OBJECTIVES: The clinical heterogeneity of frontotemporal dementia (FTD) complicates identification of biomarkers for clinical trials that may be sensitive during the prediagnostic stage. It is not known whether cognitive or...
PICALM modulates autophagy activity and tau accumulation.
Kevin Moreau, Angeleen Fleming, Sara Imarisio, Ana Lopez Ramirez, Jacob L Mercer, Maria Jimenez-Sanchez, Carla F Bento, Claudia Puri, Eszter Zavodszky, Farah Siddiqi, Catherine P Lavau, Maureen Betton, Cahir J O'Kane, Daniel S Wechsler, David C Rubinsztein
Oct 09, 2014
Animals Autophagy Autophagy-Related Protein 12 Cell Line Drosophila Endocytosis Female FIBROBLASTS Genome-Wide Association Study HEK293 Cells HeLa Cells Humans Male Mice Monomeric Clathrin Assembly Proteins Phagosomes Protein Binding RNA Small Interfering Risk Factors Small Ubiquitin-Related Modifier Proteins Transfection Vesicle-Associated Membrane Protein 2 Zebrafish tau Proteins
Fulminant corticobasal degeneration
Helen Ling, Ellen Gelpi, Karen Davey, Zane Jaunmuktane, Kin Y Mok, Edwin Jabbari, Roberto Simone, Lea R'Bibo, Sebastian Brandner, Matthew J Ellis, Johannes Attems, David Mann, Glenda M Halliday, S Al-Sarraj, J Hedreen, James W Ironside, Gabor G Kovacs, E Kovari, S Love, Jean Paul G Vonsattel, Kieren SJ Allinson, Daniela Hansen, Teisha Bradshaw, Núria Setó-Salvia, Selina Wray, Rohan de Silva, Huw R Morris, Thomas T Warner, John Hardy, Janice L Holton, Tamas Revesz
Jan 15, 2021
Corticobasal degeneration typically progresses gradually over 5-7 years from onset till death. Fulminant corticobasal degeneration cases with a rapidly progressive course were rarely reported (RP-CBD). This study aimed to...
In vivo 18F-flortaucipir PET does not accurately support the staging of progressive supranuclear palsy
Maura Malpetti, Sanne Kaalund, Kamen Tsvetanov, Timothy Rittman, Mayen Briggs, Kieren SJ Allinson, Luca Passamonti, Negin Holland, P Simon Jones, Tim Fryer, Young Hong, Antonina Kouli, W Richard Bevan-Jones, Elijah Mak, George Savulich, Maria Grazia Spillantini, Franklin I Aigbirhio, Caroline Williams-Gray, John T O'Brien, James B Rowe
Oct 12, 2021
Mitochondrial ROS control neuronal excitability and cell fate in frontotemporal dementia.
Noemí Esteras, Olga Kopach, Marta Maiolino, Vincenzo Lariccia, Salvatore Amoroso, Seema Qamar, Selina Wray, Dmitri A Rusakov, Morana Jaganjac, Andrey Y Abramov
May 31, 2021
INTRODUCTION: The second most common form of early-onset dementia-frontotemporal dementia (FTD)-is often characterized by the aggregation of the microtubule-associated protein tau. Here we studied the mechanism of tau-induced...
4R tau AMPA receptors MAPT 10+16 NMDA receptors Calcium Signaling frontotemporal dementia Glutamate Induced Pluripotent Stem Cells mitochondrial antioxidants mitochondrial reactive oxygen species Tau frontotemporal dementia Humans Induced Pluripotent Stem Cells Mitochondria Neurons Reactive Oxygen Species Receptors N-Methyl-D-Aspartate tau Proteins
Re-examining tau-immunoreactive pathology in the population
Sally Hunter, Thais Minett, Tuomo Polvikoski, Elizabeta Mukaetova-Ladinska, Carol Brayne, Cambridge City over-75s Cohort Collaboration
Aug 27, 2015
Living Neurons with Tau Filaments Aberrantly Expose Phosphatidylserine and Are Phagocytosed by Microglia.
Jack Brelstaff, Aviva M Tolkovsky, Bernardino Ghetti, Michel Goedert, Maria Grazia Spillantini
Oct 03, 2018
Tau protein forms insoluble filamentous inclusions that are closely associated with nerve cell death in many neurodegenerative diseases. How neurons die in these tauopathies is unclear. We report that living neurons with tau...
A novel Alzheimer disease locus located near the gene encoding tau protein.
G Jun, CA Ibrahim-Verbaas, M Vronskaya, J-C Lambert, J Chung, AC Naj, BW Kunkle, L-S Wang, JC Bis, C Bellenguez, D Harold, KL Lunetta, AL Destefano, B Grenier-Boley, R Sims, GW Beecham, AV Smith, V Chouraki, KL Hamilton-Nelson, MA Ikram, N Fievet, N Denning, ER Martin, H Schmidt, Y Kamatani, ML Dunstan, O Valladares, AR Laza, D Zelenika, A Ramirez, TM Foroud, S-H Choi, A Boland, T Becker, WA Kukull, SJ van der Lee, F Pasquier, C Cruchaga, D Beekly, AL Fitzpatrick, O Hanon, M Gill, R Barber, V Gudnason, D Campion, S Love, DA Bennett, N Amin, C Berr, Magda Tsolaki, JD Buxbaum, OL Lopez, V Deramecourt, NC Fox, LB Cantwell, L Tárraga, C Dufouil, J Hardy, PK Crane, G Eiriksdottir, D Hannequin, R Clarke, D Evans, TH Mosley, L Letenneur, C Brayne, W Maier, P De Jager, V Emilsson, J-F Dartigues, H Hampel, MI Kamboh, RFAG de Bruijn, C Tzourio, P Pastor, EB Larson, JI Rotter, MC O'Donovan, TJ Montine, MA Nalls, S Mead, EM Reiman, PV Jonsson, C Holmes, PH St George-Hyslop, M Boada, P Passmore, JR Wendland, R Schmidt, K Morgan, AR Winslow, JF Powell, M Carasquillo, SG Younkin, J Jakobsdóttir, JSK Kauwe, KC Wilhelmsen, D Rujescu, MM Nöthen, A Hofman, L Jones, IGAP Consortium, JL Haines, BM Psaty, C Van Broeckhoven, P Holmans, LJ Launer, R Mayeux, M Lathrop, AM Goate, V Escott-Price, S Seshadri, MA Pericak-Vance, P Amouyel, J Williams, CM van Duijn, GD Schellenberg, LA Farrer
May 21, 2019
APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP)...
A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology.
Hongjun Fu, Andrea Possenti, Rosie Freer, Yoshikazu Nakano, Nancy C Hernandez Villegas, Maoping Tang, Paula VM Cauhy, Benjamin A Lassus, Shuo Chen, Stephanie L Fowler, Helen Y Figueroa, Edward D Huey, Gail Vw Johnson, Michele Vendruscolo, Karen E Duff
Jul 26, 2019
Excitatory neurons are preferentially impaired in early Alzheimer's disease but the pathways contributing to their relative vulnerability remain largely unknown. Here we report that pathological tau accumulation takes place...
Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia.
Kamen A Tsvetanov, Stefano Gazzina, P Simon Jones, John van Swieten, Barbara Borroni, Raquel Sanchez-Valle, Fermin Moreno, Robert Laforce, Caroline Graff, Matthis Synofzik, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre de Mendonça, Fabrizio Tagliavini, Isabel Santana, Simon Ducharme, Chris Butler, Alexander Gerhard, Adrian Danek, Johannes Levin, Markus Otto, Giovanni Frisoni, Roberta Ghidoni, Sandro Sorbi, Jonathan D Rohrer, James B Rowe, GENFI Genetic FTD Initiative
Sep 14, 2020
Differential impairment of cerebrospinal fluid synaptic biomarkers in the genetic forms of frontotemporal dementia.
Aitana Sogorb-Esteve, Johanna Nilsson, Imogen J Swift, Carolin Heller, Martina Bocchetta, Lucy L Russell, Georgia Peakman, Rhian S Convery, John C van Swieten, Harro Seelaar, Barbara Borroni, Daniela Galimberti, Raquel Sanchez-Valle, Robert Laforce, Fermin Moreno, Matthis Synofzik, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James B Rowe, Rik Vandenberghe, Elizabeth Finger, Fabrizio Tagliavini, Isabel Santana, Chris R Butler, Simon Ducharme, Alexander Gerhard, Adrian Danek, Johannes Levin, Markus Otto, Sandro Sorbi, Isabelle Le Ber, Florence Pasquier, Johan Gobom, Ann Brinkmalm, Kaj Blennow, Henrik Zetterberg, Jonathan D Rohrer, GENetic FTD Initiative
Oct 01, 2022
BACKGROUND: Approximately a third of frontotemporal dementia (FTD) is genetic with mutations in three genes accounting for most of the inheritance: C9orf72, GRN, and MAPT. Impaired synaptic health is a common mechanism in all...
A robust and interpretable machine learning approach using multimodal biological data to predict future pathological tau accumulation
Zoe Kourtzi
May 09, 2022
Nicotinamide mononucleotide adenylyltransferase uses its NAD+ substrate-binding site to chaperone phosphorylated Tau.
Xiaojuan Ma, Yi Zhu, Jinxia Lu, Jingfei Xie, Chong Li, Woo Shik Shin, Jiali Qiang, Jiaqi Liu, Shuai Dou, Yi Xiao, Chuchu Wang, Chunyu Jia, Houfang Long, Juntao Yang, Yanshan Fang, Lin Jiang, Yaoyang Zhang, Shengnan Zhang, Rong Grace Zhai, Cong Liu, Dan Li
Apr 06, 2020
Alzheimer's Disease D. melanogaster NAD synthase NMNAT Biochemistry chaperone chemical biology phosphorylated Tau Tauopathy Animals Binding Sites Drosophila HSP90 Heat-Shock Proteins Homeostasis Humans Molecular Chaperones NAD Nicotinamide-Nucleotide Adenylyltransferase Phosphorylation Synapses tau Proteins
Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity.
Sanne Simone Kaalund, Luca Passamonti, Kieren SJ Allinson, Alexander G Murley, Trevor W Robbins, Maria Grazia Spillantini, James B Rowe
Feb 04, 2020
NDRG2 Expression Correlates with Neurofibrillary Tangles and Microglial Pathology in the Ageing Brain.
Motaz M Fadul, Claire J Garwood, Rachel Waller, Navonna Garrett, Paul R Heath, Fiona E Matthews, Carol Brayne, Stephen B Wharton, Julie E Simpson
Jan 10, 2020
N-myc downstream regulated gene 2 (NDRG2) Ageing brain astrocyte Neurofibrillary Tangles Aged Aged 80 and over aging Alzheimer Disease Antigens CD Antigens Differentiation Myelomonocytic Astrocytes Brain DNA Damage Excitatory Amino Acid Transporter 2 Gene Expression Regulation Glial Fibrillary Acidic Protein Glutamate-Ammonia Ligase Humans Microglia Neurofibrillary Tangles Tumor Suppressor Proteins tau Proteins
Computational Investigation of RNA A-Bulges Related to the Microtubule-Associated Protein Tau Causing Frontotemporal Dementia and Parkinsonism.
Mutations in the human tau gene result in alternative splicing of the tau protein, which causes frontotemporal dementia and Parkinsonism. One disease mechanism is linked to the stability of a hairpin within the...
Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD
Raphael Schneider, Paul McKeever, TaeHyung Kim, Caroline Graff, John Cornelis van Swieten, Anna Karydas, Adam Boxer, Howie Rosen, Bruce L Miller, Robert Laforce, Daniela Galimberti, Mario Masellis, Barbara Borroni, Zhaolei Zhang, Lorne Zinman, Jonathan Daniel Rohrer, Maria Carmela Tartaglia, Janice Robertson, Genetic FTD Initiative (GENFI)
May 10, 2018
OBJECTIVE: To determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic...
A walk through tau therapeutic strategies.
Santosh Jadhav, Jesus Avila, Michael Schöll, Gabor G Kovacs, Enikö Kövari, Rostislav Skrabana, Lewis D Evans, Eva Kontsekova, Barbara Malawska, Rohan de Silva, Luc Buee, Norbert Zilka
May 01, 2019
Tau neuronal and glial pathologies drive the clinical presentation of Alzheimer's disease and related human tauopathies. There is a growing body of evidence indicating that pathological tau species can travel from cell to cell...
Hsp70 Inhibits the Nucleation and Elongation of Tau and Sequesters Tau Aggregates with High Affinity.
Franziska Kundel, Suman De, Patrick Flagmeier, Mathew H Horrocks, Magnus Kjaergaard, Sarah L Shammas, Sophie E Jackson, Christopher M Dobson, David Klenerman
Mar 13, 2018
A152T tau allele causes neurodegeneration that can be ameliorated in a zebrafish model by autophagy induction
Autophagy neurodegeneration Proteasome Tauopathy Alleles Animals Autophagy Autophagy-Related Protein 5 Behavior Animal Disease Models Animal Embryo Nonmammalian frontotemporal dementia Heredodegenerative Disorders Nervous System Humans Kinetics Polymorphism Single Nucleotide Proteasome Endopeptidase Complex RNA Supranuclear Palsy Progressive Tauopathies Zebrafish Zebrafish Proteins tau Proteins
Hyperphosphorylated tau self-assembles into amorphous aggregates eliciting TLR4-dependent responses.
Jonathan X Meng, Yu Zhang, Dominik Saman, Arshad M Haider, Suman De, Jason C Sang, Karen Brown, Kun Jiang, Jane Humphrey, Linda Julian, Eric Hidari, Steven F Lee, Gabriel Balmus, R Andres Floto, Clare E Bryant, Justin LP Benesch, Yu Ye, David Klenerman
Jun 16, 2022
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