RT Journal Article SR Electronic T1 Is there a relation between APOE expression and brain amyloid load in Alzheimer’s disease? JF Journal of Neurology, Neurosurgery & Psychiatry JO J Neurol Neurosurg Psychiatry FD BMJ Publishing Group Ltd SP 928 OP 933 DO 10.1136/jnnp.2004.048983 VO 76 IS 7 A1 J-C Lambert A1 D Mann A1 F Richard A1 J Tian A1 J Shi A1 U Thaker A1 S Merrot A1 J Harris A1 B Frigard A1 T Iwatsubo A1 C Lendon A1 P Amouyel YR 2005 UL http://jnnp.bmj.com/content/76/7/928.abstract AB 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.