Plasma TDP‐43 in neurodegenerative diseases assayed with immunomagnetic reduction

Background TDP‐43 is a promising biomarker for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, studies on TDP‐43 in human biofluid are rare. In this work, the authors utilized an ultrasensitive technology, called immunomagnetic reduction (IMR), to develop the reagent for assaying TDP‐43. Method The preclinical performance characteristics of the TDP‐43 reagent, such as the standard curve, detection limits, assay linearity, dilution recovery range, assay reproducibility, spike recovery, reagent stability, and interference tests, were explored according to the CLSI guidelines. Plasma samples from normal controls (NC, n = 27) and from patients with frontotemporal dementia (FTD, n = 9), Alzheimer’s disease (AD, n = 34) and Parkinson’s disease (PD, n = 10) were collected for TDP‐43 assays using the IMR TDP‐43 reagent. Result The low‐detection limit of assaying TDP‐43 was 0.68 fg/ml, and the upper‐detection limit was 100 pg/ml. There was no significant interference effect when assaying TDP‐43 mixed with hemoglobin, bilirubin, intralipid, albumin, etc. The FTD patients had significantly higher levels of plasma TDP‐43 (0.419±0.193 fg/ml) compared to the NC subjects (0.163±0.097 fg/ml), AD patients (0.165±0.082 fg/ml) and PD patients (0.069±0.068 fg/ml). Through analysis of the ROC curve, the cut‐off value of plasma TDP‐43 for discriminating FTD from the other patient groups was 0.237 fg/ml, which resulted a clinical sensitivity of 0.889 and a specificity of 0.831. Conclusion These results demonstrate the feasibility of assaying plasma TDP‐43 to specifically identify FTD.