title: A new promoter polymorphism in the alpha-1-antichymotrypsin gene is a disease modifier of Alzheimer's disease.
abstract: 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) epsilon 4 allele. After manifestation of the disease the ACT TT genotype was also associated with faster cognitive decline in patients with the APOE allele epsilon 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.
authors.affiliation: Department of Experimental Pathology, School of Medicine, University of Bologna, Via S. Giacomo 14, 40126 Bologna, Italy. licastro@alma.unibo.it
authors.forename: Federico
authors.initials: F
authors.lastname: Licastro
authors.forename: Martina
authors.initials: M
authors.lastname: Chiappelli
authors.forename: Luigi M E
authors.initials: LM
authors.lastname: Grimaldi
authors.forename: Kevin
authors.initials: K
authors.lastname: Morgan
authors.forename: Noor
authors.initials: N
authors.lastname: Kalsheker
authors.forename: Elena
authors.initials: E
authors.lastname: Calabrese
authors.forename: Alistair
authors.initials: A
authors.lastname: Ritchie
authors.forename: Elisa
authors.initials: E
authors.lastname: Porcellini
authors.forename: Giuliana
authors.initials: G
authors.lastname: Salani
authors.forename: Massimo
authors.initials: M
authors.lastname: Franceschi
authors.forename: Nicola
authors.initials: N
authors.lastname: Canal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000208:ethnology; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D000514:alpha 1-Antichymotrypsin / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D000514:alpha 1-Antichymotrypsin