Article Text

Download PDFPDF
Is there a relation between APOE expression and brain amyloid load in Alzheimer’s disease?
  1. J-C Lambert1,
  2. D Mann2,
  3. F Richard1,
  4. J Tian2,
  5. J Shi2,
  6. U Thaker2,
  7. S Merrot3,
  8. J Harris4,
  9. B Frigard3,
  10. T Iwatsubo5,
  11. C Lendon4,
  12. P Amouyel1
  1. 1Unité INSERM 508, Institut Pasteur de Lille, Lille cédex, France
  2. 2Neuroscience Research Group, University of Manchester, Hope Hospital, Manchester, UK
  3. 3Centre Hospitalier Gériatrique, Wasquehal, France
  4. 4Department of Psychiatry, University of Birmingham, Birmingham, UK
  5. 5Department of Neuropathology and Neuroscience, University of Tokyo, Tokyo, Japan
  1. Correspondence to:
 Dr Jean-Charles Lambert
 unité INSERM 508, Institut Pasteur de Lille, BP 245,1 rue du professeur Calmette, 59019 Lille cédex, France;


Background: It has been proposed that, independent of the ε4 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 β-actin gene expression was determined by reverse transcriptase polymerase chain reaction in brain and lymphocytes.

Results: An inverse correlation between APOE expression level and Aβ 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 Aβ deposition was found, irrespective of APOE ε4 allele status. This effect was more pronounced in older individuals, whereas higher Aβ load appeared more closely related to ε4 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 Aβ load in Alzheimer’s disease.

  • apoE, apolipoprotein E protein
  • APP, amyloid precursor protein
  • CAA, cerebral amyloid angiopathy
  • CERAD, Consortium to Establish a Registry for Alzheimer’s Disease
  • DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders, third edition, revised
  • NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association
  • Alzheimer’s disease
  • amyloid
  • APOE expression

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Competing interests: none declared