title: Cell surface extensions associated with overexpression of Alzheimer beta/A4 amyloid.
abstract: Deposition of beta/A4 amyloid in Alzheimer disease (AD) brain parenchyma and vasculature occurs by mechanisms that are currently undefined. Similarly the potential consequences of amyloid accumulation for disrupting cellular integrity have not been addressed in detail. To investigate the possible significance of amyloid deposits for cellular viability, PC12 cells were permanently transfected with DNA coding for the beta/A4-C terminal region of the amyloid precursor protein. The DNA represented 97 amino acids of the amyloid precursor protein of which 40 amino acids were derived from the beta/A4 region. Transfected clonal cell lines and controls were examined at both the light and electron microscopic levels for morphological abnormalities. beta/A4 amyloid accumulated in the cell membrane where the peptide was located at cellular processes resembling blebs and microvilli. These specialized structures at the cell surface were over-abundant in transfected cells that overexpressed the beta/A4 peptide but not in controls. Membranous processes may be involved in the delivery of the beta/A4 peptide to the external surface of the cell of origin and release into the extracellular space. Similar surface features of cells in the AD brain, should they occur, may indicate a role for membrane-associated processes in the pathophysiology of the disorder.
authors.affiliation: Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, MA 02115.
authors.forename: G E
authors.initials: GE
authors.lastname: Maestre
authors.forename: B
authors.initials: B
authors.lastname: Tate
authors.forename: R E
authors.initials: RE
authors.lastname: Majocha
authors.forename: C A
authors.initials: CA
authors.lastname: Marotta
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D016501:Neurites / Q000648:ultrastructure*; D016716:PC12 Cells; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D004247:DNA