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 prote in (APP) immunoreactivity as a sensitive marker for impairment of fast axon al transport in the spinal cords of patients with HTLV-I-associated myelopa thy (HAM)/tropical spastic paraparesis (TSP). The results from this study s how that APP, used as a marker of early axonal damage in HAM/TSP lesions, i s more intensively expressed in areas of active-inflammatory lesions than t hose of inactive-chronic lesions. The close localization to the areas conta ining inflammation (activation of macrophage/microglia) is striking and sug gests that axonal damage is closely associated with inflammation in active- chronic lesions. Although inflammatory cell infiltration in the central ner vous system (CNS) is rarely found in inactive-chronic lesions, a few cluste rs of APP+ axons are found in the spinal cord white matter in some cases. T he presence of APP+ axons without relation to inflammatory cells in inactiv e-chronic lesions, suggest that soluble neurotoxic factors might induce axo nal 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 tr ansport may contribute to the development of disability in patients with HA M/TSP. (C) 2000 Elsevier Science B.V. All rights reserved.