TY - JOUR
T1 - Intronic CYP46 polymorphism along with ApoE genotype in sporadic Alzheimer Disease
T2 - From risk factors to disease modulators
AU - Borroni, Barbara
AU - Archetti, Silvana
AU - Agosti, Chiara
AU - Akkawi, Nabil
AU - Brambilla, Cristina
AU - Caimi, Luigi
AU - Caltagirone, Carlo
AU - Di Luca, Monica
AU - Padovani, Alessandro
PY - 2004/7
Y1 - 2004/7
N2 - Increasing biological and clinical findings argue for a link between brain cholesterol turnover and Alzheimer Disease (AD), high cerebral levels of the former increasing Aβ load. Cerebral cholesterol elimination involves two mechanisms dependent on Apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46). The aim of this study was to evaluate an intronic variation in CYP46 (intron 2, T→C) along with ApoE genotype as risk factors for AD and to establish the correlation between CYP46/ApoE polymorphism and disease progression. One-hundred and fifty-seven AD patients, who had been followed periodically through 1-year follow-up after enrolment, and 134 age- and gender-matched controls entered the study. The distribution of CYP46 genotypes was significantly different in AD compared to controls (P*C allele higher in AD patients (P*C carriers was 2.8, and in ApoE ε4 carriers was 4.05; the OR for having both CYP46 *C and ApoE ε4 was 17.75, demonstrating the their synergic effect on AD risk. In AD patients, CYP46*C along with ApoE ε4 genotype were associated with a higher cognitive decline at 1-year follow-up (P
AB - Increasing biological and clinical findings argue for a link between brain cholesterol turnover and Alzheimer Disease (AD), high cerebral levels of the former increasing Aβ load. Cerebral cholesterol elimination involves two mechanisms dependent on Apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46). The aim of this study was to evaluate an intronic variation in CYP46 (intron 2, T→C) along with ApoE genotype as risk factors for AD and to establish the correlation between CYP46/ApoE polymorphism and disease progression. One-hundred and fifty-seven AD patients, who had been followed periodically through 1-year follow-up after enrolment, and 134 age- and gender-matched controls entered the study. The distribution of CYP46 genotypes was significantly different in AD compared to controls (P*C allele higher in AD patients (P*C carriers was 2.8, and in ApoE ε4 carriers was 4.05; the OR for having both CYP46 *C and ApoE ε4 was 17.75, demonstrating the their synergic effect on AD risk. In AD patients, CYP46*C along with ApoE ε4 genotype were associated with a higher cognitive decline at 1-year follow-up (P
KW - Alzheimer Disease
KW - ApoE
KW - CYP46
KW - Rate of cognitive decline
KW - Risk factors
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UR - http://www.scopus.com/inward/citedby.url?scp=2542523048&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2003.08.004
DO - 10.1016/j.neurobiolaging.2003.08.004
M3 - Article
C2 - 15165699
AN - SCOPUS:2542523048
VL - 25
SP - 747
EP - 751
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 6
ER -