Increased neuronal Rab5 immunoreactive endosomes do not colocalize with TDP-43 in motor neuron disease

Exp Neurol. 2010 Sep;225(1):133-9. doi: 10.1016/j.expneurol.2010.06.004. Epub 2010 Jun 15.


Sporadic motor neuron disease (MND) is characterized by progressive degeneration of motor neurons and intraneuronal cytoplasmic translocation and deposition of the nuclear protein TDP-43. There is a paucity of data on the subcellular mechanisms of the nuclear-cytoplasmic trafficking of TDP-43, particularly about the precise role of the endosomal-lysosomal system (ELS). In the present study, using a neuron-specific morphometric approach, we examined the expression of the early endosomal marker Rab5 and lysosomal cathepsins B, D, F, and L as well as PAS-stained structures in the anterior horn cells in 11 individuals affected by sporadic MND and 5 age-matched controls. This was compared with the expression of ubiquitin, p62 and TDP-43 and its phosphorylated form. The principal finding was the increased expression of the endosomal marker Rab5 and lysosomal cathepsin D, and of PAS-positive structures in motor neurons of MND cases. Furthermore, the area-portion of Rab5 immunoreactivity correlated well with the intracellular accumulation of ubiquitin, p62 and (phosphorylated) TDP-43. However, double immunolabelling and immunogold electron microscopy excluded colocalization of phosphorylated TDP-43 with the ELS. These data contrast with observations on neuronal cytopathology in Alzheimer's or prion diseases where the disease-specific proteins are processed within endosomes, and suggest a distinct role of the ELS in MND.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Aged
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / ultrastructure
  • Endosomes / metabolism*
  • Endosomes / pathology*
  • Endosomes / ultrastructure
  • Female
  • Humans
  • Intracellular Fluid / chemistry
  • Intracellular Fluid / metabolism
  • Lysosomes / metabolism
  • Lysosomes / pathology
  • Lysosomes / ultrastructure
  • Male
  • Middle Aged
  • Motor Neuron Disease / metabolism*
  • Motor Neuron Disease / pathology*
  • Phosphorylation / genetics
  • Protein Transport / genetics
  • rab5 GTP-Binding Proteins / biosynthesis*
  • rab5 GTP-Binding Proteins / genetics
  • rab5 GTP-Binding Proteins / ultrastructure


  • DNA-Binding Proteins
  • rab5 GTP-Binding Proteins