title: [Evaluation of amyloid-beta by the E280A mutation in presenilin gene].
abstract: BACKGROUND
  The E280A mutation of the presenilin 1 gene has been found to be the most common associate in Alzheimers 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-beta 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-beta , as a response to gain in gamma-secretase function.
  
  
  METHODS
  Levels of systemic amyloid-beta 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-beta 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 beta -amyloid deposition. No differences were observed in the amount or location of amyloid-beta between affected and unaffected cadavers. Not increase was noted in the production of amyloid-beta 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-beta in non-neuronal peripheral tissues, or in the in vitro model. This is in contrast to the expectation in a gamma-secretase gain of function.
authors.affiliation: Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia. villegas@neurociencias.udea.edu.co
authors.forename: Andrés
authors.initials: A
authors.lastname: Villegas
authors.forename: Mónica M
authors.initials: MM
authors.lastname: Castañeda
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Arias
authors.forename: Beatriz
authors.initials: B
authors.lastname: Vieco
authors.forename: Francisco
authors.initials: F
authors.lastname: Lopera
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bedoya
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002102:Cadaver; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D053764:Presenilin-1 / Q000235:genetics*; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases