Résumé :
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The recent development of therapeutic interventions in the field of neurodegenerative diseases makes mandatory the concomitant development of biomarkers both for an earlier ascertainment of the diagnosis and for a better evaluation of the activity of a given drug. The conjunction of a better understanding of the physio pathology of the diseases and of new technologies made possible the hope for new biomarkers in body fluids or in tissues. In the amyotrophic lateral sclerosis (ALS), numbers of possible markers have been developed. Genetic markers allow describing at least one mutation which is responsible for clinical phenotypes identical to sporadic forms of the disease. However, this mutation is also responsible for clinical phenotypes which are usually recognized as non ALS patients. The recent description of the absence of immunostaining in vitro of SOD mutated tissues with anti TPD43, a marker considered as specific of the sporadic forms, makes more confused the possible translation between genetic and sporadic forms of the disease. Various attempts have been made to find possible markers of different mechanisms of the degenerative process in different body fluids, mainly the cerebrospinal fluid, or the plasma: axonal injury (mainly neurofilaments light and/or heavy chains; tau); neuroinflammation (MCP1; chemokines; cytokines such as TNFalpha); growth factors (BDNF, CNTF, GDNF, VEGF, EPO, IgF); oxidative stress; glutamate; apoptosis. However, until now, most of these studies are not convincing with large variations among individuals. These results underline the well known large heterogeneity of the disease, which makes so difficult the use of endpoints in clinical trials. Few data are available in tissue except the recent description of a possible marker in the muscle (Nogo). More recently, several attempts have been made to try to find possible markers using more refined and more accurate methods such as proteomic, metabolomic, transcriptomic, or wide genome analysis. However, despite huge efforts we have no convincing markers at the moment. Genetic markers remain the most interesting and the most convincing for a better understanding of the mechanisms underlying the neurodegenerative processes. However, their usefulness both for diagnosis or follow up of patients remains nil. Another difficulty is the possible lack of translation, at least in ALS, between genetic and sporadic forms of the disease. It seems also very urgent and necessary to associate the genetic studies with convincing clinical studies making possible a better definition of possible endophenotypes of these diseases. In this scope, it seems less promising to start from a given, predetermined, molecule. The use of large approaches, such as omic methods or wide genome screen, seems at least initially more promising. To contact the author:: vincent.meininger@psl.aphp.fr.
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