O Bugiani1. 1. IRCCS Carlo Besta, Via Celoria 11, I-20133, Milan, Italy. bugiani1@virgilio.it
Abstract
BACKGROUND: Frontotemporal degeneration (FTD) is the most common cause of dementia after Alzheimer's disease. To date, it has been addressed with intensive and intense research. OBJECTIVE: To report on the most recent findings in the biology of FTD. METHODS: Review of FTD literature. RESULTS: FTD presents with many phenotypes that span from prefrontal syndromes to lower motor neuron disease passing through temporal, parietal and extrapyramidal syndromes. FTD includes the frontotemporal lobar atrophies clinically characterised by abnormal behaviour, progressive aphasia or semantic dementia, as well as corticobasal degeneration, progressive supranuclear palsy, progressive subcortical gliosis and FTD with motor neuron disease. The molecular classification of FTD can be traced following the immunocytochemical properties of the material accumulated in neuroectodermic cells. This procedure allows the separation of FTD with tau-positive inclusions from FTD with ubiquitin-positive inclusions, and from FTD with inclusions negative for both. Genetically, seven loci (chromosomes 3p, 9q and 17q24, one locus each; 9p and 17q21, two loci each) and four genes (MAPT, PRGN, VCP, CHMP2B) have been identified. Proteins involved are tau, progranulin, VCP, CHMP2B, Progranulin TDP43, ubiquitin and the intermediate neurofilament system. Neurodegeneration is most likely due to changes in cytoskeletal structure and in ubiquitin-dependent protein degradation activity.
BACKGROUND: Frontotemporal degeneration (FTD) is the most common cause of dementia after Alzheimer's disease. To date, it has been addressed with intensive and intense research. OBJECTIVE: To report on the most recent findings in the biology of FTD. METHODS: Review of FTD literature. RESULTS:FTD presents with many phenotypes that span from prefrontal syndromes to lower motor neuron disease passing through temporal, parietal and extrapyramidal syndromes. FTD includes the frontotemporal lobar atrophies clinically characterised by abnormal behaviour, progressive aphasia or semantic dementia, as well as corticobasal degeneration, progressive supranuclear palsy, progressive subcortical gliosis and FTD with motor neuron disease. The molecular classification of FTD can be traced following the immunocytochemical properties of the material accumulated in neuroectodermic cells. This procedure allows the separation of FTD with tau-positive inclusions from FTD with ubiquitin-positive inclusions, and from FTD with inclusions negative for both. Genetically, seven loci (chromosomes 3p, 9q and 17q24, one locus each; 9p and 17q21, two loci each) and four genes (MAPT, PRGN, VCP, CHMP2B) have been identified. Proteins involved are tau, progranulin, VCP, CHMP2B, Progranulin TDP43, ubiquitin and the intermediate neurofilament system. Neurodegeneration is most likely due to changes in cytoskeletal structure and in ubiquitin-dependent protein degradation activity.
Authors: Gaia Skibinski; Nicholas J Parkinson; Jeremy M Brown; Lisa Chakrabarti; Sarah L Lloyd; Holger Hummerich; Jørgen E Nielsen; John R Hodges; Maria Grazia Spillantini; Tove Thusgaard; Sebastian Brandner; Arne Brun; Martin N Rossor; Anders Gade; Peter Johannsen; Sven Asger Sørensen; Susanne Gydesen; Elizabeth M C Fisher; John Collinge Journal: Nat Genet Date: 2005-07-24 Impact factor: 38.330
Authors: Marc Cruts; Ilse Gijselinck; Julie van der Zee; Sebastiaan Engelborghs; Hans Wils; Daniel Pirici; Rosa Rademakers; Rik Vandenberghe; Bart Dermaut; Jean-Jacques Martin; Cornelia van Duijn; Karin Peeters; Raf Sciot; Patrick Santens; Tim De Pooter; Maria Mattheijssens; Marleen Van den Broeck; Ivy Cuijt; Krist'l Vennekens; Peter P De Deyn; Samir Kumar-Singh; Christine Van Broeckhoven Journal: Nature Date: 2006-07-16 Impact factor: 49.962
Authors: Nigel J Cairns; Eileen H Bigio; Ian R A Mackenzie; Manuela Neumann; Virginia M-Y Lee; Kimmo J Hatanpaa; Charles L White; Julie A Schneider; Lea Tenenholz Grinberg; Glenda Halliday; Charles Duyckaerts; James S Lowe; Ida E Holm; Markus Tolnay; Koichi Okamoto; Hideaki Yokoo; Shigeo Murayama; John Woulfe; David G Munoz; Dennis W Dickson; Paul G Ince; John Q Trojanowski; David M A Mann Journal: Acta Neuropathol Date: 2007-06-20 Impact factor: 17.088
Authors: Ian R A Mackenzie; Eileen H Bigio; Paul G Ince; Felix Geser; Manuela Neumann; Nigel J Cairns; Linda K Kwong; Mark S Forman; John Ravits; Heather Stewart; Andrew Eisen; Leo McClusky; Hans A Kretzschmar; Camelia M Monoranu; J Robin Highley; Janine Kirby; Teepu Siddique; Pamela J Shaw; Virginia M-Y Lee; John Q Trojanowski Journal: Ann Neurol Date: 2007-05 Impact factor: 10.422
Authors: Kirk C Wilhelmsen; Mark S Forman; Howard J Rosen; Loren I Alving; Jill Goldman; Jennie Feiger; James V Lee; Samantha K Segall; Joel H Kramer; Catherine Lomen-Hoerth; Katherine P Rankin; Julene Johnson; Heidi S Feiler; Michael W Weiner; Virginia M-Y Lee; John Q Trojanowski; Bruce L Miller Journal: Arch Neurol Date: 2004-03
Authors: Sara Rollinson; Julie S Snowden; David Neary; Karen E Morrison; David M A Mann; Stuart M Pickering-Brown Journal: Neurosci Lett Date: 2007-03-24 Impact factor: 3.046
Authors: J S Snowden; S M Pickering-Brown; I R Mackenzie; A M T Richardson; A Varma; D Neary; D M A Mann Journal: Brain Date: 2006-09-26 Impact factor: 13.501
Authors: N Parkinson; P G Ince; M O Smith; R Highley; G Skibinski; P M Andersen; K E Morrison; H S Pall; O Hardiman; J Collinge; P J Shaw; E M C Fisher Journal: Neurology Date: 2006-06-28 Impact factor: 9.910
Authors: Geidy E Serrano; Marwan N Sabbagh; Lucia I Sue; Jose A Hidalgo; Julie A Schneider; Barry J Bedell; Vivianna M Van Deerlin; Eunran Suh; Haruhiko Akiyama; Abhinay D Joshi; Michael J Pontecorvo; Mark A Mintun; Thomas G Beach Journal: J Alzheimers Dis Date: 2014 Impact factor: 4.472