engleski

Identifying biomarkers in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Frontotemporal dementia (FTD) is the second most common cause of presenile dementia after Alzheimer’s disease. Amyotrophic lateral sclerosis (ALS) is the most common adult-onset fatal motor neuron disease. Both, FTD and ALS are neurodegenerative disorders pathologically characterized by lesions composed of disease-specific misfolded proteins. Their clinical syndromes often have overlapping features such as impaired cognition demonstrated in about 50% of ALS patients, making ante mortem prediction of pathology challenging. Therefore, sensitive and reliable biomarkers that reflect the underlying disease process are urgently needed, and are a prerequisite for an accurate diagnosis and the development of novel disease-modifying therapeutic strategies. The neuropathology associated with most FTD and/or ALS is characterized by abnormal cellular aggregation of transactive response DNA-binding 43 protein (TDP-43), fused in sarcoma/translated in liposarcoma (FUS/TLS), tau protein or unindentified ubiquitinated protein (atypical FTLD-U). Most cases of ALS are sporadic, but about 10% are familial ALS. Genes known to cause familial ALS (FALS) are superoxide dismutase 1 (SOD1), ANG encoding angiogenin, TARDP encoding TDP-43, FUS, and optineurin (OPTN). However, these genetic defects occur in only about 20–30% of cases of FALS, and most genes causing FALS are unknown. A pathogenic role of TDP-43 and FUS is indicated in possibly all types of ALS, except for SOD-1 linked ALS, which may have a pathogenic pathway distinct from other types of ALS. A great proportion of FTD cases are familial, up to 40%, resulting from null mutations in GRN gene encoding progranulin, and mutations in MAPT gene encoding tau protein. Several missense mutations have been identified in GRN but yet to be determined as pathogenic. Therefore, TDP-43 and FUS-proteinopaties are possibly novel targets for the development of therapeutics in this spectrum of diseases

amyotrophic lateral sclerosis; biomarkers; early diagnosis

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