title: Association study between Alzheimer's disease and genes involved in Abeta biosynthesis, aggregation and degradation: suggestive results with BACE1.
abstract: BACKGROUND
  Amyloid beta-peptide (Abeta) biosynthesis, aggregation and degradation constitute three important steps to consider in the study of pathological mechanisms involved in Alzheimer's disease (AD). Several proteins have been suggested as involved in each of these processes: proteolytic cleavage of the amyloid precursor protein by the beta-site APP cleaving enzyme (BACE), increased amyloid fibril formation by the activity of the acetylcholinesterase (ACHE gene), and degradation of Abeta aggregates by the plasmin system have been exhaustively documented.
  
  
  METHODS
  A case-control design was used to evaluate the possible association between candidate genes involved in these three processes and AD. We analysed three polymorphisms located at the BACE1 gene, one polymorphism at the ACHE gene, and two variants located at the tissue plasminogen activator and plasminogen activator inhibitor-1 (genes TPA and PAI- 1, respectively), both part of the plasmin system.
  
  
  RESULTS
  We found an association between BACE1 exon 5 GG genotype and AD (age-and gender-adjusted odds ratio = 2.14, P =0.014). Although a similar association was reported previously by Nowotny and collaborators only in subjects carrying the epsilon4-allele of the apolipoprotein E gene (APOE), we did not detect this effect. However,when we combined our results with those previously reported, a clear increase of the risk to develop AD appeared in subjects carrying both the BACE1 exon 5 GG genotype and the APOE epsilon4-allele (crude OR = 2.2, P = 0.004).
  
  
  CONCLUSIONS
  These data suggest a possible genetic relation between BACE1 and AD.
authors.affiliation: Unitat de Biologia Evolutiva, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Doctor Aiguader 80, 08003 Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimón
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
authors.forename: Francesc
authors.initials: F
authors.lastname: Calafell
authors.forename: Mercè
authors.initials: M
authors.lastname: Boada
authors.forename: Lluís
authors.initials: L
authors.lastname: Tàrraga
authors.forename: David
authors.initials: D
authors.lastname: Comas
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000110:Acetylcholinesterase / Q000235:genetics; D000368:Aged; D000483:Alleles; D020087:Alu Elements / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016321:Dental Care for Aged; D010450:Endopeptidases; D005091:Exons; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D016254:Mutagenesis, Insertional; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D000110:Acetylcholinesterase; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D010959:Tissue Plasminogen Activator; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human