International meeting of the French society of neurology 2013 Frontotemporal lobar degeneration and amyotrophic lateral sclerosis: Molecular similarities and differences De´ge´ne´rescences lobaires fronto-temporales et scle´rose late´rale amyotrophique : similiarite´s et diffe´rences mole´culaires M. Neumann a, * ,b a Department of Neuropathology, University of Tu ¨ bingen, Calwerstr 3, 72076 Tu ¨ bingen, Germany b DZNE, German Center for Neurodegenerative Diseases, Paul-Ehrlich-Str. 15-17, 72076 Tu ¨ bingen, Germany r e v u e n e u r o l o g i q u e x x x ( 2 0 1 3 ) x x x – x x x * Correspondence. E-mail address : Manuela.Neumann@dzne.de. i n f o a r t i c l e Article history: Received 16 June 2013 Accepted 16 July 2013 Available online xxx Keywords: Frontotemporal lobar degeneration (FTLD) Frontotemporal dementia (FTD) Amyotrophic lateral sclerosis (ALS) TDP-43 FUS C9ORF72 Mots cle ´s : Scle ´ rose late ´ rale amyotrophique De ´ mence frontotemporale TDP-43 FUS C9ORF72 a b s t r a c t In the last years, new disease proteins and genes have been identified in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), leading to a dramatic shift in our understanding of the molecular mechanisms underlying both conditions. The vast majority of FTLD and ALS are characterized by the abnormal accumulation of TDP-43, including genetic forms associated with mutations in the genes C9ORF72, GRN, TARDBP and VCP. The overlap in pathology and of genetic factors, particularly C9ORF72 as common cause of ALS and FTLD, provides molecular evidence that both conditions represent a spectrum of diseases sharing similar pathomechanisms. Accumulation of the protein FUS defines another subset of FTLD and ALS. However, here some striking differences have been identified. All members of the FET family (FUS, EWS, TAF15) are co-accumulating with their nuclear import receptor Transportin in FTLD-FUS which is usually not associated with FUS mutations, whilst ALS-FUS is almost always associated with FUS mutations and reveals only FUS aggregates. Together with recent data demonstrating differences in the arginine methylation status of FUS in FTLD-FUS and ALS-FUS, these findings strongly imply at least partially distinct underlying disease mechanisms in these molecular subtypes of ALS and FTLD. # 2013 Elsevier Masson SAS. All rights reserved. r e ´s u m e ´ Ces dernie ` res anne ´es l’identification de nouvelles anomalies prote ´ iques et ge ´ne ´ tiques concernant a ` la fois les de ´ge ´ne ´ rescences lobaires fronto-temporales (DLFT) et la scle ´ rose late ´ rale amyotrophique (SLA) a amene ´a ` un changement radical dans notre compre ´ hension des me ´ canismes mole ´ culaires sous-jacents. La grande majorite ´ des DLFT et des SLA est caracte ´ rise ´e par l’accumulation anormale de TDP-43, y compris les formes ge ´ne ´ tiques associe ´es aux mutations des ge ` nes C9ORF72, GRN, TARDBP et VCP. Ce recouvrement a ` la NEUROL-1138; No. of Pages 6 Please cite this article in press as: Neumann M, Frontotemporal lobar degeneration and amyotrophic lateral sclerosis: Molecular similarities and differences. Revue neurologique (2013), http://dx.doi.org/10.1016/j.neurol.2013.07.019 Available online at www.sciencedirect.com 0035-3787/$ – see front matter # 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.neurol.2013.07.019