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6 results on '"LICASTRO F"'

4. Elevated Plasma Levels of -1-Anti-Chymotrypsin in Age-Related Cognitive Decline and Alzheimers Disease: A Potential Therapeutic Target

Author

Porcellini, E., Davis, E., Chiappelli, M., Ianni, E., Di Stefano, G., Forti, P., Ravaglia, G., and Licastro, F.

Abstract

-1-antichymotrypsin (ACT), is an acute phase protein and a protease inhibitor produced by the liver and brain. ACT is involved in the pathogenesis of Alzheimers disease (AD), since elevated ACT concentration was found in cerebrospinal fluid (CSF) and brain from AD. ACT has also been shown to influence amyloid deposition in vitro and in animal models of AD. In this investigation 830 healthy controls, 69 subjects with cognitive impairment and not dementia (CIND), 53 patients with severe clinical AD and 142 patients with mild AD were investigated. Plasma levels of ACT were measured with a new competitive immune enzyme linked immune-assay (ELISA). ACT levels were higher in AD patients than in CIND or controls. An age dependent increase of plasma ACT was present in both healthy elderly and CIND. Patients with mild clinical AD were followed up for two years and stratified according to the rate of clinical deterioration. CT plasma levels were elevated in AD patients that showed an accelerated rate of cognitive deterioration during the follow up; this increment being prominent in AD with the Apolipoprotein E (APOE) 4 allele. Therefore, increased peripheral ACT levels in APOE 4 positive patients appear to predict an accelerated clinical progression. Plasma ACT might be used as a surrogate marker to monitor the conversion of pre-dementia stages to AD and the progression of the disease. The development of compounds able to interfere with the ACT biological activity (protease inhibition and/or promotion of amyloid deposition) might have therapeutic relevance for the disease.

Published
2008

5. Gene-gene and gene - clinical factors interaction in acute myocardial infarction: a new detailed risk chart

Author

Martina Chiappelli, Massimo Buscema, Elisa Porcellini, F. Garoia, Federico Licastro, Roberto Ferrari, Gianluca Campo, Enzo Grossi, Licastro F, Chiappelli M, Porcellini E, Campo G, Buscema M, Grossi E, Garoia F, and Ferrari R

Subjects
Male, Genotype, Interleukin-1beta, Vascular Endothelial Growth Factor C, Myocardial Infarction, Single-nucleotide polymorphism, Pilot Projects, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, chemistry.chemical_compound, Gene interaction, Risk Factors, Drug Discovery, Diabetes Mellitus, Medicine, SNP, Humans, Age of Onset, Gene, Genetic Association Studies, Aged, Pharmacology, Genetics, business.industry, Genetic heterogeneity, Interleukin-6, Cholesterol, HDL, Age Factors, Promoter, Middle Aged, Vascular endothelial growth factor, chemistry, Case-Control Studies, Immunology, Acute Disease, Female, Hydroxymethylglutaryl CoA Reductases, business
Abstract

Aims: The complex pathogenesis of acute myocardial infarction (AMI) implicates phenotypic and genetic heterogeneity. In this pilot case-control study single nucleotide polymorphism (SNP) in several inflammatory genes, such as interleukin (IL)-1β, IL-6, IL- 10, α-1-antichymotrypsin (ACT), tumor necrosis factor alpha (TNF)-α and interferon gamma (IFN)-γ genes along with SNPs of genes regulating vascular functions (vascular endothelial growth factor; VEGF) and cholesterol synthesis (hydroxy-methyl-glutaryl CoA reductase; HMGCR) were investigated. Methods: Patients were genotyped with RT-PCR technique and data were analyzed with a new mathematical algorithm named Auto Contractive Map. Results: The Auto Contractive Map (AutoCM), was applied in AMI patients with the aim to detect and evaluate the relationships among genetic factors, clinical variables and classical risk factors. Genes were selected because their strong regulatory effect on inflammation and SNP in these gene were located in the promoter region. In the connectivity map generated by AutoCM a group of variables was directly linked with the AMI status; these were: gender (male), early age at onset (50-65 years), HMGCR gene (CC wild type genotype), IL-1βCT, IL-6 GG and VEGF CC genotypes. This direct link suggested a possible pathogenetic association with AMI. Other genetic, clinical and phenotypic variables were associated to the disease under a statistically defined hierarchy showed in the new connectivity map generated by AutoCM. Conclusion: These analyses suggested that genotypes of few inflammatory genes, a SNP in HMGCR gene, middle age, gender, low HDL and diabetes were very informative variables to predict the risk of AMI.

Published
2009

6. Elevated plasma levels of alpha-1-anti-chymotrypsin in age-related cognitive decline and Alzheimer's disease: a potential therapeutic target.

Author

Porcellini E, Davis EJ, Chiappelli M, Ianni E, Di Stefano G, Forti P, Ravaglia G, and Licastro F

Subjects
Age Factors, Aged, Aged, 80 and over, Alleles, Alzheimer Disease drug therapy, Alzheimer Disease genetics, Alzheimer Disease metabolism, Apolipoprotein E4 genetics, Biomarkers blood, Case-Control Studies, Cognition Disorders drug therapy, Cognition Disorders genetics, Cognition Disorders metabolism, Drug Delivery Systems, Female, Follow-Up Studies, Humans, Male, Severity of Illness Index, Alzheimer Disease blood, Cognition Disorders blood, Enzyme-Linked Immunosorbent Assay methods, alpha 1-Antichymotrypsin blood
Abstract

alpha-1-antichymotrypsin (ACT), is an acute phase protein and a protease inhibitor produced by the liver and brain. ACT is involved in the pathogenesis of Alzheimer's disease (AD), since elevated ACT concentration was found in cerebrospinal fluid (CSF) and brain from AD. ACT has also been shown to influence amyloid deposition in vitro and in animal models of AD. In this investigation 830 healthy controls, 69 subjects with cognitive impairment and not dementia (CIND), 53 patients with severe clinical AD and 142 patients with mild AD were investigated. Plasma levels of ACT were measured with a new competitive immune enzyme linked immune-assay (ELISA). ACT levels were higher in AD patients than in CIND or controls. An age dependent increase of plasma ACT was present in both healthy elderly and CIND. Patients with mild clinical AD were followed up for two years and stratified according to the rate of clinical deterioration. CT plasma levels were elevated in AD patients that showed an accelerated rate of cognitive deterioration during the follow up; this increment being prominent in AD with the Apolipoprotein E (APOE) epsilon 4 allele. Therefore, increased peripheral ACT levels in APOE 4 positive patients appear to predict an accelerated clinical progression. Plasma ACT might be used as a surrogate marker to monitor the conversion of pre-dementia stages to AD and the progression of the disease. The development of compounds able to interfere with the ACT biological activity (protease inhibition and/or promotion of amyloid deposition) might have therapeutic relevance for the disease.

Published
2008
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