TY - JOUR
T1 - A new promoter polymorphism in the alpha-1-antichymotrypsin gene is a disease modifier of Alzheimer's disease
AU - Licastro, Federico
AU - Chiappelli, Martina
AU - Grimaldi, Luigi M E
AU - Morgan, Kevin
AU - Kalsheker, Noor
AU - Calabrese, Elena
AU - Ritchie, Alistair
AU - Porcellini, Elisa
AU - Salani, Giuliana
AU - Franceschi, Massimo
AU - Canal, Nicola
PY - 2005/4
Y1 - 2005/4
N2 - Increased levels of alpha-1-antichymotrypsin (ACT), a protease inhibitor and an acute phase protein, have been found in the brain and peripheral blood of patients with Alzheimer's disease (AD). Patients from northern Italy with a clinical diagnosis of probable AD, and patients with early onset AD (EOAD) from UK with AD neuropathological diagnosis were genotyped for a new polymorphism in the promoter region of the ACT gene which has been shown to affect ACT expression. A subset of patients with clinical AD from northern Italy was also followed up for 2 years and monitored for cognitive decline. The ACT TT promoter genotype was associated with an increased risk of EOAD independently from the presence of the apolipoprotein E (APOE) ε 4 allele. After manifestation of the disease the ACT TT genotype was also associated with faster cognitive decline in patients with the APOE allele ε 4. The ACT gene appears to influence the early clinical development of the disease, and the interaction of the ACT and APOE genes affects clinical progression of AD.
AB - Increased levels of alpha-1-antichymotrypsin (ACT), a protease inhibitor and an acute phase protein, have been found in the brain and peripheral blood of patients with Alzheimer's disease (AD). Patients from northern Italy with a clinical diagnosis of probable AD, and patients with early onset AD (EOAD) from UK with AD neuropathological diagnosis were genotyped for a new polymorphism in the promoter region of the ACT gene which has been shown to affect ACT expression. A subset of patients with clinical AD from northern Italy was also followed up for 2 years and monitored for cognitive decline. The ACT TT promoter genotype was associated with an increased risk of EOAD independently from the presence of the apolipoprotein E (APOE) ε 4 allele. After manifestation of the disease the ACT TT genotype was also associated with faster cognitive decline in patients with the APOE allele ε 4. The ACT gene appears to influence the early clinical development of the disease, and the interaction of the ACT and APOE genes affects clinical progression of AD.
KW - Alpha-1-antichymotrypsin gene
KW - Alzheimer's disease risk
KW - APOE ε alleles
KW - Cognitive decline
KW - Promoter polymorphism
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U2 - 10.1016/j.neurobiolaging.2004.05.001
DO - 10.1016/j.neurobiolaging.2004.05.001
M3 - Article
C2 - 15653173
AN - SCOPUS:19944429724
VL - 26
SP - 449
EP - 453
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 4
ER -