DOWN-REGULATION OF THE AMYLOID PROTEIN-PRECURSOR OF ALZHEIMERS-DISEASE BY ANTISENSE OLIGONUCLEOTIDES REDUCES NEURONAL ADHESION TO SPECIFIC SUBSTRATA

The hallmark of Alzheimer's disease is the cerebral deposition of amyl oid which is derived from the amyloid precursor protein (APP). The fun ction 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 substr ate-specific interaction between neurons and extracellular matrix comp onents 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 whethe r an intermediary pathway is involved. (C) 1997 Elsevier Science B.V.