Abstract
BackgroundTwo 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.ResultspTDP43 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.ConclusionThis 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.
Highlights
Two commercially available TAR DNA Binding protein 43 (TDP43) antibodies are currently in use for the neuropathological classification of FTLD-TDP cases into pathological subtypes
The presence of abnormal TDP43 protein deposition is a pathological feature of motor neuron disease (MND) and frontotemporal lobar degeneration with TDP43-positive inclusions (FTLDTDP) and a variety of FTLD-TDP subtypes are recognized based on the morphology and anatomical distribution of both neuronal inclusions and dystrophic neurites [2,3,4] (Figure 1)
In two cases, a greater proportion of dystrophic neurites (DN) were observed in comparison to neuronal cytoplasmic inclusions (NCIs) and long DNs were not present, a proportion of observers incorrectly classified these cases with subtype C
Summary
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. 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. There are, at present, two types of commercially available TDP43 antibodies used to neuropathologically identify and classify the abnormal inclusions and neurites into the different FTLD-TDP subtypes – phosphorylated (pTDP43) and non-phosphorylated (iTDP43) TDP43 antibodies. The present study aimed to compare the severity of pathological lesions identified with two of the most commonly used pTDP43 and iTDP43 antibodies in a cohort of 14 FTLD-TDP cases, and to assess the accuracy and interobserver reliability of these antibodies for the purpose of FTLD-TDP subtyping
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