title: Is there a relation between APOE expression and brain amyloid load in Alzheimer's disease?
abstract: BACKGROUND
  It has been proposed that, independent of the epsilon4 allele, APOE promoter polymorphisms (-491 A/T and -219 G/T) may be risks factor for Alzheimer's disease by modulating APOE expression.
  
  
  OBJECTIVE
  To measure the level of APOE expression in Alzheimer's disease.
  
  
  METHODS
  Brains were obtained at necropsy from 114 patients with early and late onset sporadic Alzheimer's disease in Greater Manchester (UK) during years 1986 to 2001. Total RNA was extracted from 84 brains. Purified lymphocytes were obtained from fresh blood from 16 probable Alzheimer cases from Lille (France). APOE and beta-actin gene expression was determined by reverse transcriptase polymerase chain reaction in brain and lymphocytes.
  
  
  RESULTS
  An inverse correlation between APOE expression level and A beta loads was observed. As previously described and extended to 114 cases here, an association between the -219 TT genotype and a higher level of parenchymal A beta deposition was found, irrespective of APOE epsilon4 allele status. This effect was more pronounced in older individuals, whereas higher A beta load appeared more closely related to epsilon4 in the younger age group (cut off point at the median age at death (72.5 years)). The -219 TT genotype was associated with a decrease in APOE expression. There was a 60% decrease in APOE expression in lymphocytes from probable Alzheimer cases v controls (p = 0.01).
  
  
  CONCLUSIONS
  In the oldest individuals, reduced APOE expression, modulated in part by -219 G/T polymorphism, may influence risk and constitute a determinant A beta load in Alzheimer's disease.
authors.affiliation: Unité INSERM 508, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59019 Lille cédex, France. jean-charles.lambert@pasteur-lille.fr
authors.forename: J-C
authors.initials: JC
authors.lastname: Lambert
authors.forename: D
authors.initials: D
authors.lastname: Mann
authors.forename: F
authors.initials: F
authors.lastname: Richard
authors.forename: J
authors.initials: J
authors.lastname: Tian
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.forename: U
authors.initials: U
authors.lastname: Thaker
authors.forename: S
authors.initials: S
authors.lastname: Merrot
authors.forename: J
authors.initials: J
authors.lastname: Harris
authors.forename: B
authors.initials: B
authors.lastname: Frigard
authors.forename: T
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: C
authors.initials: C
authors.lastname: Lendon
authors.forename: P
authors.initials: P
authors.lastname: Amouyel
mesh_terms: D000199:Actins / Q000235:genetics; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013223:Statistics as Topic
chemical_list: D000199:Actins; D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D012333:RNA, Messenger