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β-Amyloid formation by myocytes of leptomeningeal vessels

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Abstract

Ultrastructural study of the leptomeningeal vessels of three subject with Alzheimer's disease (AD) shows that β-amyloid deposits in the media of arteries and arterioles are produced by smooth muscle cells. It appears that the soluble β-protein secreted by sarcolemmal vesicles of the muscle cell polymerizes into amyloid fibrils in basal lamina. Myocytes trapped in amyloid deposits degenerate and die. The most common and severe degeneration of smooth muscle cells in seen in the external and medial zone of the vascular media. In more advanced stages of amyloidotic changes, the internal zone of media is also involved. The media of vessels with severe changes consists of amyloid deposits and cell debris. Amyloid fibrils around the dead myocytes also undergo degradation. They lose their fibrillar appearance and become floccular, granular, amorphous proteinous material; however, this material is continually positive in immunostaining for β-amyloid. This study suggests that amyloid formation by smooth muscle cells involves a secretory path. Our data indicate that the smooth muscle cell secretes nonfibrillar β-protein or β-protein containing peptides and that conversion of nonfibrillar into fibrillar β-amyloid takes place in the environment of the basement membrane.

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Supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and a grant from the National Institutes of Health, National Institute of Aging No. PO1-AGO-4220

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Wisniewski, H.M., Wegiel, J. β-Amyloid formation by myocytes of leptomeningeal vessels. Acta Neuropathol 87, 233–241 (1994). https://doi.org/10.1007/BF00296738

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