Axonal damage revealed by accumulation of beta-amyloid precursor protein in HTLV-I-associated myelopathy.
We investigated the localization and extent of beta-amyloid precursor protein (APP) immunoreactivity as a sensitive marker for impairment of fast axonal transport in the spinal cords of patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The results from this study show that APP, used as a marker of early axonal damage in HAM/TSP lesions, is more intensively expressed in areas of active-inflammatory lesions than those of inactive-chronic lesions. The close localization to the areas containing inflammation (activation of macrophage/microglia) is striking and suggests that axonal damage is closely associated with inflammation in active-chronic lesions. Although inflammatory cell infiltration in the central nervous system (CNS) is rarely found in inactive-chronic lesions, a few clusters of APP+ axons are found in the spinal cord white matter in some cases. The presence of APP+ axons without relation to inflammatory cells in inactive-chronic lesions, suggest that soluble neurotoxic factors might induce axonal changes in the CNS of HAM/TSP. The occasional myelinated fibers in the anterior and posterior spinal roots in lower thoracic to lumbar levels had APP+ axons, suggesting that spinal nerve roots can be affected in HAM/TSP, especially in lower thoracic to lumbar levels. Impairment of fast axonal transport may contribute to the development of disability in patients with HAM/TSP.
Umehara
F
F
The Third Department of Internal Medicine, Kagoshima University School of Medicine, Sakuragaoka 8-35-1, Kagoshima, Japan. umehara@med6.kufm.kagoshima-u.ac.jp
Abe
M
M
Koreeda
Y
Y
Izumo
S
S
Osame
M
M
D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000032:analysis*; D001370:Axonal Transport / Q000502:physiology; D015415:Biomarkers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology* / Q000503:physiopathology; D015493:Paraparesis, Tropical Spastic / Q000473:pathology* / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers