Genetics and neurochemical biomarkers in ALS and FTLD
Feneberg E., Hübers A., Weishaupt JH., Ludolph A., Otto M.
Both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are progressive neurodegenerative diseases. In ALS, neurodegeneration results in progressive paralysis of muscles and finally in respiratory insufficiency. FTLD, on the other hand, progressively affects behavior, speech, and in some cases the motor system. Over recent years, some clinical overlapping of these syndromes with their common histopathology of aggregated TDP-43 in the cytoplasm of neurons resulted in the hypothesis that both syndromes are parts of a clinical as well as pathophysiological continuum. As a first step, mutations of the TDP-43 gene have been identified as possible molecular mechanism. Furthermore, a pathological repeat expansion of chromosome 9 - C9orf72 - is associated with 25-30 percent of all genetically determined cases of ALS and about 11 percent of the FTLD cases in Europe. However, 20% of the sporadic cases also have a C9orf72 expansion. Particularly in asymptomatic mutation carriers and in sporadic cases, the diagnosis at an early stage of the disease and reliable classification of the symptoms of ALS and FTLD is usually difficult. Therefore, it would be desirable to develop reliable and specific biomarkers that allow valid diagnosis and evaluation of prognosis. © Georg Thieme Verlag KG Stuttgart New York.