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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 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.

Язык: Английский

---

Deep learning-based automated segmentation for the quantitative diagnosis of cerebral small vessel disease via multisequence MRI

Frontiers in Neurology, Год журнала: 2025, Номер 16

Опубликована: Май 27, 2025

Objective Existing visual scoring systems for cerebral small vessel disease (CSVD) cannot assess the global lesion load accurately and quantitatively. We aimed to develop an automated segmentation method based on deep learning (DL) quantify typical neuroimaging markers of CSVD multisequence magnetic resonance imaging (MRI). Materials methods MRI scans from internal (July 2018 July 2022) external (November 2012 January 2015) datasets were analyzed. A DL-based was developed evaluate quantitative volumes white matter hyperintensity (WMH), microbleeds (CMBs), lacunes, enlarged perivascular spaces (EPVSs) according results. Dice other metrics used access DL Pearson correlation coefficients analysis, differences in marker among different scores assessed via analysis variance (ANOVA). Finally, a Z score calculated represent CSVD-related brain burden. Results total 105 patients (64.8 ± 7.4 years, 70 males) 58 (68.2 6.8 29 evaluated. The values WMH, CMBs, EPVSs dataset 0.85, 0.74, 0.76, 0.75, respectively. positive between manual approach results excellent (overall = 0.968, 0.978, 0.948, 0.947, respectively). predicted showed significant groups with ( p < 0.001). reflecting burden also correlated well widely recognized Conclusion An model four MRI, providing strong basis further research.

Язык: Английский

---

ApoE and Cerebrovascular Disease

Опубликована: Янв. 1, 2025

Язык: Английский

---

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

Sleep And Breathing, Год журнала: 2024, Номер 29(1)

Опубликована: Ноя. 29, 2024

Язык: Английский

---