The present invention is in the field of transactive response DNA binding protein with a molecular weight of 43 kDa (TARDB or also TDP-43). The invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or an antigen-binding fragment or a derivative thereof and uses thereof. The present invention provides means and methods to diagnose, prevent, alleviate and/or treat a disorder and/or abnormality associated with misfolded TDP-43 including but not limited to frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD, sporadic and familial), and/or Parkinson's disease (PD). The present invention provides modified conformation-specific antigenic peptides and peptide fragments derived from the TDP-43 protein and the antibodies obtainable by said peptides or fragments for use in the diagnosis, prevention, alleviation and/or treatment of TDP-43-related disorders and/or abnormalities.
