Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication.

Beta-amyloid (Abeta) causes detachment of N1E-115 neuroblastoma cells by acting as a scaffold for cell-associated plasminogen activation.

Kranenburg O, Bouma B, Gent YY, Aarsman CJ, Kayed R, Posthuma G, Schiks B, Voest EE, Gebbink MF

Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.

A major component of neuritic plaques in brain tissue of Alzheimer's disease patients is the beta-amyloid peptide (Abeta). Accumulation of Abeta has been associated with increased neuronal cell death and cognitive decline. We have previously shown that amyloid peptides like Abeta bind tissue-type plasminogen activator (tPA) and stimulate plasmin production. Here we investigated how Abeta regulates plasmin formation by N1E-115 neuroblastoma cells and the effects of Abeta-mediated plasmin formation on cell attachment and cell survival. We find that Abeta induces excessive cell-associated plasmin generation that causes cell detachment. Cell detachment is inhibited by carboxypeptidase B (CPB), an enzyme that blocks plasmin formation by cleaving off C-terminal lysine residues. Plasmin and CPB control Abeta-induced cell detachment independently of direct effects on cell viability. Abeta40 as well as oligomeric and fibrillar forms of Abeta42 stimulated tPA-mediated plasminogen activation and cell detachment. Our results suggest that plasmin-mediated cell detachment could contribute to the pathological effects of Abeta in diseased brain.

Published 1 March 2005 in Mol Cell Neurosci, 28(3): 496-508.
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