Is there a relation between APOE expression and brain amyloid load in Alzheimer's disease?
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.
Lambert
J-C
JC
Unité INSERM 508, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, 59019 Lille cédex, France. jean-charles.lambert@pasteur-lille.fr
Mann
D
D
Richard
F
F
Tian
J
J
Shi
J
J
Thaker
U
U
Merrot
S
S
Harris
J
J
Frigard
B
B
Iwatsubo
T
T
Lendon
C
C
Amouyel
P
P
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
D000199:Actins; D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D012333:RNA, Messenger