title: Down-regulation of the amyloid protein precursor of Alzheimer's disease by antisense oligonucleotides reduces neuronal adhesion to specific substrata.
abstract: The hallmark of Alzheimer's disease is the cerebral deposition of amyloid which is derived from the amyloid precursor protein (APP). The function of APP is unknown but there is increasing evidence for the role of APP in cell-cell and/or cell-matrix interactions. Primary cultures of murine neurons were treated with antisense oligonucleotides to down-regulate APP. This paper presents evidence that APP mediates a substrate-specific interaction between neurons and extracellular matrix components collagen type I, laminin and heparan sulphate proteoglycan but not fibronectin or poly-L-lysine. It remains to be determined whether this effect is the direct result of APP-matrix interactions, or whether an intermediatry pathway is involved.
authors.affiliation: Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: E J
authors.initials: EJ
authors.lastname: Coulson
authors.forename: G L
authors.initials: GL
authors.lastname: Barrett
authors.forename: E
authors.initials: E
authors.lastname: Storey
authors.forename: P F
authors.initials: PF
authors.lastname: Bartlett
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: C L
authors.initials: CL
authors.lastname: Masters
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003470:Culture Media; D005109:Extracellular Matrix / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D051379:Mice; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D015345:Oligonucleotide Probes / Q000494:pharmacology
chemical_list: D016564:Amyloid beta-Protein Precursor; D016375:Antisense Elements (Genetics); D003470:Culture Media; D015345:Oligonucleotide Probes