DN2M » Alzheimer

Alzheimer

Alzheimer’s disease (AD) is the most common neurodegenerative disease, which progressively and ineluctably leads to massive brain neuronal death. Neuropathologically, AD is characterized by two brain lesions: amyloid deposits which result from the aggregation of a peptide of 40-42 amino-acids generated from its precursor APP and neurofibrillary tangles which are degenerating neurons composed of filaments made of the microtubule-associated Tau proteins. Despite significant advances in understanding the mechanisms of disease, treatments to delay onset or slow progression appear some way off. For instance, different Aß modifiers have failed in phase III trials. A real input is needed for improving early diagnosis and for developing new approaches targeting amyloid and Tau pathologies. After age 65, the likelihood of developing dementia roughly doubles every five years. The worrying medical, social and economic scale of AD is in marked contrast to the lack of solutions available to efficiently tackle this major threat to individuals and society. This challenge has been taken into account in France since 2008 through a five-year national plan aimed at fostering research in the AD field by promoting the emergence of additional research units and strengthening pre-existing ones with international visibility. In DN2M, a close collaboration between clinicians and research scientists has allowed for a focus on AD research with several teams involved in this research (P. Amouyel, R. Bordet, L. Buée, R. Cecchelli, G. Lippens, F. Pasquier). To confirm this momentum and ensure its durability, several of DN2M research units, which are among the very best and most productive in France, have decided to combine their multidisciplinary skills, from basic to social concepts, to create a unique laboratory of excellence (LabEx). The Labex, named DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease), integrates various basic approaches, from agnostic genomics to highly sophisticated biological models, and combine clinical approaches with social and ethical concerns. Its aim is to join forces in a unique laboratory with a common research programme and a major critical mass ready to overcome some obstacles of AD research, and to accelerate discovery and translation of innovative solutions from new potential drug targets into socially and ethically appropriate answers. It relies upon the presence of international leaders in complementary AD basic research fields, bringing together genomics and epidemiology of aging diseases (UMR744 Inserm, P. Amouyel, Lille), physiological deregulations, molecular and cellular biology (UMR837 Inserm, L. Buée, Lille), and biophysics (UMR8576 CNRS G. Lippens, Villeneuve d’Ascq). To go further in this multidisciplinary approach, internationally renowned clinicians and key opinion leaders involved in translational research (Lille MRRC, F. Pasquier, Lille), motivated social and healthcare researchers (EA1059, P. Antoine, Lille) are also fully integrated in a common research project. Other national laboratories with specific expertise (outside DN2M) have also joined DISTALZ such UMR6097 CNRS, F. Checler, Sophia Antipolis (amyloid related pathologies) and EA1610 E Hirsch, Paris (ethics specialists).

4 selected publications:

  • Ando K, Dourlen P, Sambo AV, Bretteville A, Bélarbi K, Vingtdeux V, Eddarkaoui S, Drobecq H, Ghestem A, Bégard S, Demey-Thomas E, Melnyk P, Smet C, Lippens G, Maurage CA, Caillet-Boudin ML, Verdier Y, Vinh J, Landrieu I, Galas MC, Blum D, Hamdane M, Sergeant N, Buée L. Tau pathology modulates Pin1 post-translational modifications and may be relevant as biomarker. Neurobiol Aging. 2012 Aug 25.
  • Deramecourt V, Lebert F, Maurage CA, Fernandez-Gomez FJ, Dujardin S, Colin M, Sergeant N, Buée-Scherrer V, Clot F, Ber IL, Brice A, Pasquier F, Buée L. Clinical, Neuropathological, and Biochemical Characterization of the Novel Tau Mutation P332S. J Alzheimers Dis. 2012 Jan 1;31(4):741-9.
  • Gabelle A, Dumurgier D, Vercruysse O, Paquet C, Bombois S, Laplanche JL, Peoc’h K, Schraen S, Buée L, Pasquier F, Hugon J, Touchon J, Lehmann S. Impact of the 2008-2012 French Alzheimer Plan on the use of CSF biomarkers in Research Memory Center: The PLM study. J Alzheimers Dis, in press.
  • Lambert JC, Grenier-Boley B, Harold D, Zelenika D, Chouraki V, Kamatani Y, Sleegers K, Ikram MA, Hiltunen M, Reitz C, Mateo I, Feulner T, Bullido M, Galimberti D, Concari L, Alvarez V, Sims R, Gerrish A, Chapman J, Deniz-Naranjo C, Solfrizzi V, Sorbi S, Arosio B, Spalletta G, Siciliano G, Epelbaum J, Hannequin D, Dartigues JF, Tzourio C, Berr C, Schrijvers EM, Rogers R, Tosto G, Pasquier F, Bettens K, Van Cauwenberghe C, Fratiglioni L, Graff C, Delepine M, Ferri R, Reynolds CA, Lannfelt L, Ingelsson M, Prince JA, Chillotti C, Pilotto A, Seripa D, Boland A, Mancuso M, Bossù P, Annoni G, Nacmias B, Bosco P, Panza F, Sanchez-Garcia F, Del Zompo M, Coto E, Owen M, O'Donovan M, Valdivieso F, Caffara P, Scarpini E, Combarros O, Buée L, Campion D, Soininen H, Breteler M, Riemenschneider M, Van Broeckhoven C, Alpérovitch A, Lathrop M, Trégouët DA, Williams J, Amouyel P. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease. Mol Psychiatry. 2012 Mar 20. doi: 10.1038/mp.2012.14.