Is the urea cycle involved in Alzheimer's disease?
Since previous observations indicated that the urea cycle may have a role in the Alzheimer's disease (AD) process, we set out to quantify the expression of each gene involved in the urea cycle in control and AD brains and establish whether these genes could be genetic determinants of AD. We first confirmed that all the urea cycle enzyme genes are expressed in the AD brain. The expression of arginase 2 was greater in the AD brain than in the control brain. The presence of the rare arginase 2 allele rs742869 was associated with an increase in the risk of AD in men and with an earlier age-at-onset for both genders. None of the other genes in the pathway appeared to be differentially expressed in the AD brain or act as genetic determinants of the disease.
Hansmannel
Franck
F
INSERM U744, Lille, France.
Sillaire
Adeline
A
Kamboh
M Ilyas
MI
Lendon
Corinne
C
Pasquier
Florence
F
Hannequin
Didier
D
Laumet
Geoffroy
G
Mounier
Anais
A
Ayral
Anne-Marie
AM
DeKosky
Steven T
ST
Hauw
Jean-Jacques
JJ
Berr
Claudine
C
Mann
David
D
Amouyel
Philippe
P
Campion
Dominique
D
Lambert
Jean-Charles
JC
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D001119:Arginase / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014508:Urea / Q000378:metabolism*
D014508:Urea; C477631:ARG2 protein, human; D001119:Arginase