Plexin D1 accumulation in the spinal motor neurons of patients with amyotrophic lateral sclerosis.

BACKGROUND

Plexin D1 in endothelial cells (ECs) in the spinal cord (SC) has emerged as a key protein in spinal motor neuron (MN) maturation. Here, we pathologically investigated plexin D1 expression in the SCs of patients with sporadic amyotrophic lateral sclerosis (sALS) to clarify the association between plexin D1 expression in ECs and MN degeneration.

METHODS

We measured plexin D1 expression in the ECs of lumbar SC tissue samples from 11 patients with sALS and 8 age- and sex-matched patients with other non-inflammatory neurological diseases (OND) by immunohistochemistry. Additionally, the number and percentage of plexin D1-positive MNs in lumbar MNs were assessed in each case. We also evaluated the immunoreactivity of TAR DNA binding protein (TARDBP) in plexin D1-positive MNs.

RESULTS

Immunohistochemistry showed that there was no obvious difference in plexin D1 expression in ECs between sALS and OND cases. Unexpectedly, plexin D1 accumulation was greater in MNs of patients with sALS compared with those with OND. The number and percentage of plexin D1-positive MNs in patients with sALS were significantly greater than in patients with OND (median [interquartile range], 6 [1-11] vs. 1 [0-3.3], p = 0.0349; and 12.9 % [5.5-15.5] vs. 1.1 % [0-3.5], p = 0.0032, respectively). Plexin D1-positive MNs showed TARDBP cytoplasmic mislocalization and aggregation.

CONCLUSIONS

Plexin D1 was similarly expressed in ECs between sALS and OND cases, but accumulated in the degenerated MNs of patients with sALS. Plexin D1 accumulation in MNs may provide new insights into the mechanism of MN degeneration in ALS.