Plasma alpha1-antichymotrypsin in Alzheimer's disease; relationships with APOE genotypes.
Inflammatory processes are thought to be important contributors to the pathogenesis of Alzheimer's disease (AD). alpha1-antichymotrypsin (ACT) is a proteinase inhibitor characteristic of acute-phase inflammation and has been identified in amyloid plaques. We analyzed the plasma ACT levels in a sample of subjects with late-onset AD and correspondent controls. Plasma ACT was higher in AD patients (62.8 +/- 20.2 mg/dl) than in controls (58.8 +/- 18.1 mg/dl), but not significantly (P = 0.13). In the AD patients regression analysis showed a positive linear relationship between ACT levels and duration of the disease (P = 0.037). Increased ACT concentrations (64.6 +/- 21.2 mg/dl) were also found in patients with greater cognitive impairment (MMSE scores < 20), but since this factor depends on the duration of the disease as well, our present data seem to indicate a complex relationship involving elevated ACT levels, disease duration and cognitive impairment. Plasma ACT was found to differ significantly according to APOE genotypes (P = 0.017), the highest levels being associated to E3-E3 homozygotes (66.1 +/- 17.8 mg/dl) and the lowest to E4-E3 subjects (53.1 +/- 18.2 mg/dl). In patients not carrying APOE*4 allele the ACT levels were higher than in controls (P = 0.014), and the relationship between ACT and disease duration was stronger than that observed in the total AD sample (P = 0.003), but it was absent in those carrying APOE*4 (P = 0.67). Taken together our results seem to suggest that inflammation is a relevant factor in AD pathogenesis for subjects with E3-E3 and E3-E2 genotypes but less important for APOE*4 carrying subjects.
Scacchi
R
R
CNR Center of Evolutionary Genetics and Department of Genetics and Molecular Biology, University "La Sapienza,", Rome, Italy. Scacchi@AXCASP.CASPUR.IT
Ruggeri
M
M
Gambina
G
G
Martini
M C
MC
Ferrari
G
G
Corbo
R M
RM
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D000514:alpha 1-Antichymotrypsin / Q000097:blood* / Q000235:genetics
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D000514:alpha 1-Antichymotrypsin