Improved detection of pre-symptomatic, non-central nervous system TDP-43 pathology in amyotrophic lateral sclerosis using RNA aptamer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract A recently developed TDP-43 RNA aptamer (TDP-43 APT ) with greater sensitivity and specificity for detecting pathological TDP-43, compared to currently available antibodies, has revealed novel pathologies in ALS, including early nuclear aggregation preceding disease symptoms. Moreover, whilst ALS traditionally been considered a of the central nervous system (CNS), non-CNS manifestations are gaining increasing awareness. Employing an antibody approach detect pathologically phosphorylated we previously uncovered pre-symptomatic, systemic pathology archived tissue, taken during life. Here, using two tools, (i) identify (ii) situ hybridisation probes directed splice target ( Stathmin-2 demonstrate concurrent loss function, re-examined tissues from variety organ systems this cohort ante-mortem tissue people who went on develop ALS. Amongst organs evidence aggregation, loss-of-function, occurring prior motor symptom onset, were colon, skin, muscle, blood vessels, gallbladder, lymph nodes. Cell types affected include sebocytes, endothelial cells, peripheral neuronal dendritic chondrocytes - all cells shared cell linage neural crest, implying neurodevelopmentally-defined cell-type specific predisposition pathology. This predisposition, along identified mobile, circulating inflammatory (T-cells macrophages) may help guide early, pre-symptomatic biopsy biomarker development. Our findings extend number outside CNS symptoms, showing is common feature affecting that readily accessible biopsy. We propose skin gastro-intestinal tract provide most promising potential ease biopsy, applications diagnosis monitoring emergence amongst general at-risk populations. Graphical Abstract: detects patients diagnosis. A) Cartoon depicting with, without, detected by aptamer. B) Timeline years onset could be node, gastrointestinal tissues.

Language: Английский

The association between small vessel disease and obstructive sleep apnea: a peak width of skeletonized mean diffusivity-based study

Sleep And Breathing, Journal Year: 2024, Volume and Issue: 29(1)

Published: Nov. 29, 2024

Language: Английский