AMYLOID PRECURSOR PROTEIN (APP) EXPRESSION IN MULTIPLE-SCLEROSIS LESIONS

The amyloid precursor protein (APP) is rapidly induced in reactive gli al cells in response to several pathological stimuli including inflamm ation. In the present study, observations previously made in animal mo dels of autoimmune central nervous system inflammation have been exten ded to the analysis of multiple sclerosis (MS) lesions. A total of thi rty fresh-frozen tissue blocks from six histopathologically normal con trol and six MS eases have been examined immunocytochemically with mon oclonal antibodies directed against either C- or N-terminal epitopes o f APP. Histopathological evaluation of disease progression was based o n hematoxylin-eosin and oil red O staining and immunocytochemistry for T cells, macrophages/microglia, astrocytes, and oligodendrocytes. In control cases, APP immunoreactivity was generally low and confined to blood vessel walls, oligodendrocytes in white, and neurons in grey mat ter. In actively demyelinating plaques, however, levels of APP immunor eactivity were high, localised on T lymphocytes, foamy macrophages, ac tivated microglia, and reactive astrocytes including astrocytic proces ses. In more chronic lesions, levels of APP immunoreactivity were gene rally lower than in acute lesions, mainly found on reactive astrocytes , their processes and a few macrophages/microglia depending on the sta ge of plaque development. In addition, a few 14E-positive oligodendroc ytes and, moreover, numerous axons exhibited APP immunoreactivity, whi ch was particularly pronounced with anti-C-terminal antibodies. These results demonstrate that APP is induced on reactive glial cells but al so on T lymphocytes during demyelination. The extent of APP expression appears to be correlated to histopathological lesion development and thus suggests that APP detection serves as a sensitive marker for dise ase progression in MS. (C) 1995 Wiley-Liss, Inc.