Classification of FTLD-TDP cases into pathological subtypes using antibodies against phosphorylated and non-phosphorylated TDP43

Background: Two commercially available TDP43 antibodies (phosphorylated or pTDP43, non-phosphorylated or iTDP43) are currently in use for the neuropathological classification of FTLD-TDP cases into pathological subtypes. To date, no studies have performed direct comparisons between these TDP43 antibodies to determine if they identify the same FTLD-TDP subtypes. The reliability of subtype classification with the use of either of these antibodies has also not been investigated. The present study compares the severity of pathological lesions identified with pTDP43 and iTDP43 in a cohort of 14 FTLD-TDP cases, and assesses the accuracy and inter-observer reliability found with either of these antibodies. Results: pTDP43 identified a greater severity of pathological inclusions across FTLD-TDP cases in comparison to iTDP43 and a higher inter-observer of subtype classification was found with this antibody. Conclusion: This study demonstrates a higher consistency across independent observers in the pathological subtyping of FTLD-TDP cases with the use of a pTDP43 antibody in comparison to the iTDP43 antibody, and corroborates the use of pTDP43 for pathological classification of FTLD-TDP cases.