The angiotensin 1-converting enzyme insertion (I)/deletion (D) polymorphism does not influence the extent of amyloid or tau pathology in patients with sporadic Alzheimer's disease.
An insertion (I)/deletion (D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene has, in some studies, been associated with increased risk for Alzheimer's disease (AD), and functionally the enzyme has been implicated in the degradation of amyloid beta protein (Abeta). We have investigated the frequency of the I/D polymorphism in a clinic-based and autopsy-confirmed series of cases of AD, and investigated what impact the I/D polymorphism in ACE gene might have on the extent of Abeta and tau pathology in the frontal cortex in the autopsy-confirmed series. We found no differences in I/D allele or genotype frequencies between the clinic-based and autopsy-confirmed AD cases, or between the pooled clinic-based and autopsy-confirmed AD cases and a series of normal control subjects. Moreover, Abeta (Abeta(40) and Abeta(42)) load, tau load or extent of amyloid angiopathy did not differ between D/D, I/D and I/I genotype groups, though Abeta(42) load tended to be higher in bearers of I/I genotype (compared to D/D genotype). Neither age at onset nor duration of illness differed according to genotype. We conclude therefore that the frequency of ACE I-allele is not increased in AD and, in autopsy-confirmed AD cases, possession of the ACE I allele has no impact upon the pathology of AD, at least in terms of the amount of Abeta or tau deposited in the brain.
Lendon
C L
CL
Department of Psychiatry, University of Birmingham, Birmingham B15 2QZ, UK.
Thaker
U
U
Harris
J M
JM
McDonagh
A M
AM
Lambert
J-C
JC
Chartier-Harlin
M-C
MC
Iwatsubo
T
T
Pickering-Brown
S M
SM
Mann
D M A
DM
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012016:Reference Values; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D004251:DNA Transposable Elements; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D007703:Peptidyl-Dipeptidase A