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Plasma levels of alpha1-antichymotrypsin (ACT) and interleukin-1beta (IL-1beta) were increased in patients with probable Alzheimer's disease (AD). A common polymorphism within ACT and IL-1beta genes affected plasma levels of ACT or IL-1beta, and AD patients with the ACT T,T or IL-1beta T,T genotype showed the highest levels of plasma ACT or IL-1beta, respectively. The concomitant presence of the ACT T,T and IL-1beta T,T genotypes increased the risk of AD (odds ratio: 5.606, confidence interval: 1.654-18.996) and decreased the age at onset of the disease.

Overexpression of the pluripotent cytokine interleukin-1 (IL-1) by microglial cells correlates with formation of neuritic beta-amyloid plaques in Alzheimer's disease (AD). We evaluated polymorphisms in the genes coding for the IL-1alpha, IL-1beta, and IL-1 receptor antagonist cytokines, and tested their association with the occurrence and age at onset of sporadic AD. We found a strong association between the IL-1A T/T genotype and AD onset before 65 years of age (odds ratio, 4.86), with carriers of this genotype showing an onset of disease 9 years earlier than IL-1A C/C carriers. A weaker association with the age at onset was also shown for the IL-1B and IL-1RN genes. These data suggest either a direct effect of the IL-1 gene family, mainly IL-1A, on the clinical onset of AD, or a linkage dysequilibrium with an unknown locus relevant to AD on chromosome 2.

Alzheimer disease (AD) patients with both sporadic and familial forms of AD and non-demented controls were genotyped for common polymorphisms in the signal peptide for alpha-1-antichymotrypsin (ACT) gene and in two different regions of apolipoprotein E (APOE) gene. The ACT TT genotype was over-represented (P = 0.025) in patients with early onset of sporadic AD. In this patient's group ACT TT genotype conferred a significant crude odds ratio for the disease (OR = 2.09; 95% CI = 1.09-4.00, P = 0.025). After adjustment for the APOE epsilon4 and APOE -491 genotypes, logistic regression analysis confirmed that the ACT TT genotype resulted independently associated with early onset AD (adjusted OR = 2.56; 85% CI = 1.3-5.2, P = 0.009). The frequency of APOE epsilon4 allele was increased in AD, as expected (OR = 5.92, 95% CI = 3.60-9.70, P = 0.0001). On the contrary, the APOE -491 A/T genotypes were not associated with AD. No preferential association of the APOE epsilon4 allele or APOE -491 A/T genotypes with ACT A/T alleles was observed in AD. Present findings indicated that subjects with ACT TT genotype had an increased risk of developing AD and suggested that this genotype influenced the risk of an early onset of the disease by affecting the production of ACT molecules.

Plasma concentrations of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), C reactive protein (CRP) and alpha-1-antichymotrypsin (ACT) in 145 patients with probable Alzheimer's disease (AD) and 51 non-demented controls were measured. To investigate the cellular activation of peripheral immune system, plasma levels of neopterin were also investigated. Plasma levels of IL-1 were detectable in 17 patients with AD (13%) and only in one control (2%) and average levels of IL-1 were higher in AD patients than in controls (p < 0.001). IL-6 plasma levels were detectable in a higher proportion of AD and controls (53% and 27%, respectively), and were increased in patients with AD (p < 0.001). Plasma levels of ACT were increased in patients with AD (p < 0.001) and CRP levels were in the normal range. Plasma levels of neopterin were slightly lower in AD patients than in controls, but differences were not statistically significant. No significant correlation was observed between IL-1 and IL-6 levels or neopterin and cytokine levels in plasma from AD patients. Plasma levels of ACT negatively correlated with cognitive performances, as assessed by the mini mental state examination (MMSE; R = -0.26, p < 0.02) and positively correlated with the global deterioration state (GDS) of AD patients (R = 0.30, p < 0.007). Present findings suggested that detectable levels of circulating cytokines and increased ACT might not be derived by activation of peripheral immune system of AD patients. Detection of these molecules might be used for monitoring the progression of brain inflammation associated with AD

Although its main biological function is still unknown, the prion protein is involved in normal synaptic function.1Interestingly, the presence of a valine (V), replacing a methionine (M) at codon 129 of the prion protein gene (PRNP), has been associated with poor performance in cognitive tests in a large cohort of aged, non-demented, French people.2 Accordingly, this polymorphic gene represents a suitable candidate for an association with Alzheimer's disease, a dementing disorder characterised by neuronal degeneration and synaptic loss. To assess whether the PRNP V/M codon129 polymorphism—alone or in combination with polymorphisms in the apolipoprotein (APO)E3 and interleukin (IL)-1α4 genes, already shown to be associated with Alzheimer's disease—affects the occurrence or clinical features of the disease, we performed a case-control study in a cohort of Italian patients with sporadic Alzheimer's disease and age matched healthy controls. Venous blood was collected from 212 Italian patients (130 women, 82 men; mean (SD) age at disease onset 68.3 (8.0) years) affected by clinically probable Alzheimer's disease, according to McKhann's criteria. Patients were also divided into those with early disease onset (⩽65 years; 72 patients; mean (SD) age at disease onset 57.0 (7.5) years), and those with a late onset (>65 years; 140 patients; mean (SD) age …

The APOE e4 allele influences the occurrence of AD by lowering the age at disease onset.1 A case–control study of two (Spanish and North American) populations suggested an e4-independent association between an A/T polymorphism in the APOE regulatory region ( APOE −491) and sporadic AD,2 stronger in Spanish than in North American patients, thus suggesting genetic heterogeneity. Subsequent observations in different populations have been conflicting,3-6 ranging from a much weaker e4-independent association of APOE −491 and AD (alone3 or in association with other APOE polymorphisms4) to no5 or even a protective effect6 on the development of AD. So far, no association has been reported between this polymorphism and the age at AD onset. To explore this issue, we examined APOE −491 and e polymorphisms in Italian patients with AD and control subjects. A total of 358 white patients (age at disease onset 67.3 ± 9.3 [mean ± SD] years) affected by clinically probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria7 were enrolled. Patients were divided into those with an early onset (EO …