Biochemical and clinical characterization of TDP-43 as a diagnostic marker for FTLD with TDP-pathology.

Frontotemporal lobar degeneration (FTLD) is the second most common early-onset dementia, after Alzheimer's disease (AD). Given that FTLD indeed mostly affects middle-aged individuals, this debilitating disease has a dramatic effect on the patients' personal as well as professional life. The differential diagnosis of dementia based on a clinical diagnosis and with the help of AD biomarkers in cerebrospinal fluid is still suboptimal. Unfortunately, well-characterized and validated diagnostic markers for FTLD do not yet exist. With the discovery of TAR DNA-binding protein of 43 kDa (TDP-43) as the major disease protein in 50-60% of this clinically and genetically heterogeneous group of FTLD patients, a potential diagnostic marker for FTLD-TDP was identified. The current project aims to (1) generate new TDP-43 antibodies and characterize TDP-43; (2) develop an immunoassay to quantify TDP-43 in biological samples and (3) assess its diagnostic potential, for which samples from confirmed FTLD-TDP and AD patients will be used. If successful, this project will provide new tools (well-characterized TDP-43 antibodies and an immunoassay) for researchers to unravel the TDP-43 pathogenesis, leading to new research hypotheses and possible therapeutic ventures. By applying the TDP-43 immunoassay as a tool to identify FTLD-TDP patients, we hope to improve (differential) dementia diagnostics as well as contribute to progress within the field of other TDP-pathologies.

Keywords:DEMENTIA, FRONTOTEMPORAL DEMENTIA, FRONTOTEMPORAL LOBAR DEGENERATION, BIOMARKER

Disciplines:Diagnostics, Laboratory medicine, Neurosciences, Medicinal products, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing