BibTex format
@article{Manchinu:2026:10.1016/j.nbd.2026.107473,
author = {Manchinu, MF and Congiu, M and Massidda, M and Borghero, G and Marongiu, J and Marzi, I and Maschio, A and Rallo, V and Serra, M and Porcedda, C and Etzi, M and Palmas, MF and Angius, A and Sogos, V and Pateri, MI and Steri, M and Coroneo, V and De, Simone A and Cossu, G and Chiti, F and Carta, AR},
doi = {10.1016/j.nbd.2026.107473},
journal = {Neurobiol Dis},
title = {PBMC DEG/miRNA biomarkers of TDP-43 pathology in ALS.},
url = {http://dx.doi.org/10.1016/j.nbd.2026.107473},
volume = {226},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Amyotrophic lateral sclerosis (ALS) lacks reliable, disease-specific, and minimally invasive biomarkers, representing a major barrier to early diagnosis and patient stratification. The primary aim of this translational pilot study was to identify a disease-specific, TDP-43-related, gene-microRNA (miRNA) signature in peripheral blood mononuclear cells (PBMCs) of ALS patients with potential diagnostic value. To this end, we first identified differentially expressed disease-specific genes (dsDEGs) using a TDP-43-based rat model of ALS, generated by stereotaxic infusion of full-length (FL) TAR DNA-binding protein 43 (TDP-43) into the motor cortex. Transcriptomic profiling of the motor cortex revealed candidate dsDEGs, which were subsequently validated by RT-qPCR in motor cortex, spinal cord, and PBMCs from the same animals. To assess translational relevance, expression levels of these dsDEGs were analyzed in PBMCs from early- to mid-stage ALS patients and matched healthy controls, while disease specificity was evaluated using Parkinson's disease (PD) samples. In parallel, conserved miRNAs predicted to target the identified dsDEGs were examined in both rat and human PBMCs. Five dsDEGs, Mctp1, Penk, Mt2A, Drd1, and Rasgrp2, were consistently dysregulated across central and peripheral tissues in the TDP-43 rat model. RT-qPCR analysis of human PBMCs confirmed significant and selective dysregulation of these genes in ALS, but not in PD, supporting disease specificity. Moreover, exposure of human neuroblastoma cells and healthy PBMCs to TDP-43 recapitulated the ALS-like expression changes. Computational and experimental analyses identified seven conserved miRNAs targeting these dsDEGs, of which four were significantly downregulated in ALS PBMCs, supporting a coordinated regulatory network. Receiver operating characteristic (ROC) analyses demonstrated strong discriminative performance for both the gene signature (AUC 0.87-1.00) and the associated miRNAs (AUC 0.95-1.00). Togeth
AU - Manchinu,MF
AU - Congiu,M
AU - Massidda,M
AU - Borghero,G
AU - Marongiu,J
AU - Marzi,I
AU - Maschio,A
AU - Rallo,V
AU - Serra,M
AU - Porcedda,C
AU - Etzi,M
AU - Palmas,MF
AU - Angius,A
AU - Sogos,V
AU - Pateri,MI
AU - Steri,M
AU - Coroneo,V
AU - De,Simone A
AU - Cossu,G
AU - Chiti,F
AU - Carta,AR
DO - 10.1016/j.nbd.2026.107473
PY - 2026///
TI - PBMC DEG/miRNA biomarkers of TDP-43 pathology in ALS.
T2 - Neurobiol Dis
UR - http://dx.doi.org/10.1016/j.nbd.2026.107473
UR - https://www.ncbi.nlm.nih.gov/pubmed/42251967
VL - 226
ER -