Abstract

VILLEGAS, Andrés et al. Evaluation of amyloid-b by the E280A mutation in presenilin gene . Biomédica [online]. 2007, vol.27, n.3, pp.372-384. ISSN 0120-4157.

Introduction. The E280A mutation of the presenilin 1 gene has been found to be the most common associate in Alzheimer’s patients with a family history of this disease. Presenilin 1 is a critical component of the g-secretase complex and plays an essential role in the production of amyloid-b peptide. This peptide has been strongly associated with the physiopathology of the disease. Objective. The E280A mutation in the presenilin 1 was investigated for increased production of amyloid-b , as a response to gain in g-secretase function. Materials and methods. Levels of systemic amyloid-b were measured with congo red staining and immuno-histochemistry of the tissues of affected cadavers, compared with non-affected cadavers. The 40 and 42 amino acid amyloid-b levels were quantified by ELISA assay in CHO cell cultures. The amyloid precursor protein expressed by the cultures was detected by transfection with the cDNAs of presenilin 1 carrying the M146L, E280A, DE9 y L392V mutations. Results. Protein deposits were found in all tissues investigatged, but only a few with b -amyloid deposition. No differences were observed in the amount or location of amyloid-b between affected and unaffected cadavers. Not increase was noted in the production of amyloid-b from the CHO cells transfected with cDNA from any of the mutations of presenilin 1. Conclusions. The E280A mutation in the presenilin 1 gene was not associated with the increased production of amyloid-b in non-neuronal peripheral tissues, or in the in vitro model. This is in contrast to the expectation in a g-secretase gain of function.

Keywords : amyloid beta-protein; mutation/genetics; presenilin-1; Alzheimer disease; congo red.

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