Background: The nuclear clearance and cytoplasmic aggregation of splicing repressor TAR DNA/RNA-binding protein-43 (TDP-43) occur in approximately 50% of Alzheimer's disease (AD) cases and about 45% of frontotemporal dementia (FTD). However, it is not clear how early such mechanism occurs in AD and FTD as there is no method of detecting TDP-43 dysregulation in living individuals. Since the loss of nuclear TDP-43 leads to cryptic exon inclusion, we propose that cryptic exon-encoded peptides may be detected in patient biofluids as biomarkers of TDP-43 loss of function.
View Article and Find Full Text PDFBackground: TDP-43 nuclear clearance and cytoplasmic aggregation occur in an estimated 30-60% of cases of Alzheimer's disease (AD), but this pathology can currently only be established at autopsy. Nuclear clearance of TDP-43 leads to inclusion of cryptic exons in pre-mRNA, some of which are spliced in-frame and translated into proteins carrying novel cryptic exon-encoded epitopes. We developed a Meso Scale Discovery (MSD) ELISA against the TDP-43-associated cryptic neoepitope within the HDGFL2 protein and found significantly elevated levels of this cryptic neoepitope in biofluids of presymptomatic ALS-FTD (Irwin et al.
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December 2025
There are approximately 220 million (about 12% regional prevalence) adults living with diabetes mellitus (DM) with its related complications, and morbidity knowingly or unconsciously in the Western Pacific Region (WP). The estimated healthcare cost in the WP and Malaysia was 240 billion USD and 1.0 billion USD in 2021 and 2017, respectively, with unmeasurable suffering and loss of health quality and economic productivity.
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