Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease.
BACKGROUND
Multiple genes have been provisionally associated with Alzheimer's disease, including the coding polymorphisms in exons 8 and 13 in the low density lipoprotein receptor gene (LDLR), situated on chromosome 19p13.2.


METHODS
The sample groups consisted of 180 AD patients and 141 control spouses. We carried out genotyping of LDLR8 and LDLR13.


RESULTS
The LDLR8 GG genotype was common, found in 84% of the unaffected control subjects and 91% of the AD patients in our study. There was a ninefold elevation in risk associated with GG:CC versus A- and T- among APOE4+ subjects when compared with APOE4- subjects (odds ratio 9.3; 95% confidence interval 1.8 to 48.2). With the additional information on LDLR polymorphism, we defined an overall 12 fold elevation in risk for APOE4 in combination with LDLR GG:CC (11.9; 2.8 to 50.0; Fisher's exact test, p = 0.0002; standard power 0.999), compared with other subjects lacking all three of these polymorphisms.


CONCLUSIONS
These results imply a functional interaction between ApoE and LDL receptor proteins that determines risk for Alzheimer's disease.
Cheng
D
D
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Huang
R
R
Lanham
I S
IS
Cathcart
H M
HM
Howard
M
M
Corder
E H
EH
Poduslo
S E
SE
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D020033:Protein Isoforms; D011973:Receptors, LDL