Fig. 1

TDP-43 axonal pathology. An illustrative map of a motor neuron with annotations for previous observations of axonal TDP-43 pathologies in human patients. Brettschneider et al., reported TDP-43 pathology in spinal motor neurons and their neurites in postmortem spinal cord sections from ALS patients. Altman et al., Riva et al., and Kurashige et al., reported TDP-43 and phosphorylated-TDP-43 pathologies in distal nerve biopsies, and in intramuscular nerves within muscle biopsies of pre-diagnosed ALS patients. Arrowhead in image of Kurashige et al., indicates accumulation of pTDP-43 in intramuscular nerve bundles of sALS patient (Rabbit polyclonal pTDP-43 antibody; 22309–1-AP, pSer409/410, Proteintech). Kushirage et al., have also validated their findings with an additional pTDP-43 antibody (not shown; mouse monoclonal pTDP-43 antibody (TIP-PTD-M01, pSer409/410, CosmoBio). Arrows in image of Riva et al., indicate accumulation of pTDP-43 in large axons within motor nerve biopsies. Arrow in inset indicates accumulation of pTDP-43 in Schwann cells as well (Rabbit polyclonal pTDP-43 antibody; 22309–1-AP, pSer409/410, Proteintech). Authors have validated their observations with another antibody (not shown; anti-TDP-43 rabbit polyclonal (1:700, 10782–2-AP, Proteintech). Brettschnider et al., used two types of antibodies for detecting pTDP-43 in spinal cord samples: pTDP-43 pSer409/410 rabbit polyclonal antibody (CAC-TIP-PTD-P07; CosmoBio), and pTDP-43 pSer409/410 rat monoclonal antibody developed by Dr. M Neumann [30]. Altman et al., used two types of antibodies to detect TDP-43 and pTDP-43 accumulation in intramuscular nerves: Rabbit polyclonal pTDP-43 antibody; 22309–1-AP, pSer409/410, Proteintech, and Rabbit polyclonal TDP-43 antibody; 10782–2-AP, Proteintech. Images were adapted from original publications [20, 26, 27, 31]