RESUMO
BACKGROUND: Apolipoprotein A1 (apoA1) is the major apolipoprotein constituent of the high-density lipoprotein (HDL) and is involved in reverse cholesterol transport. Variation in the apoA1 gene might influence the function of the protein and, thus, brain cholesterol metabolism, leading to an increased risk for Alzheimer's disease (AD). AIM: In the current report, we investigated the role of the functional apoA1 polymorphism (-75 G/A) as a genetic risk factor for AD in a Tunisian population. METHODS: 173 AD patients and 150 healthy controls were studied. RESULTS: No association was found between this genetic variation in apoA1 gene and the risk of AD. The presence of the (-75 G/A) A allele appeared, however, to be associated with lower levels of cerebrospinal fluid Aß42 and HDL cholesterol levels in sera. CONCLUSION: Our data support the observation that apoA1 polymorphism influences cholesterol metabolism and Aß42 deposition in the brain.
RESUMO
Recent evidences indicate that polymorphisms within the promoter region of the vascular endothelial growth factor (VEGF) gene may elevate the risk for Alzheimer's disease (AD). To further investigate, we have analyzed association between promoter polymorphisms of the VEGF gene in 93 AD patients and age and sex matched 113 controls from Tunisian population. The distribution of genotype and allele frequencies of the VEGF (-2578C/A) and (-1154G/A) polymorphisms did not differ significantly between AD and control groups (p>0.05). In the subgroup of ApoE varepsilon4 carriers, the -2578A was observed to be significantly higher in the AD patients than in the control individuals. After adjusting the data by gender, age and the ApoE varepsilon4 status using logistic regression, the -2578A allele was found to increase the risk for sporadic AD by 1.7-fold. The present study provides the evidence that the -2578A allele may be associated with the development of AD in the individuals with ApoE varepsilon4 allele. In addition, AD patients carrying the -2578A allele had lower Abeta42 (p=0.029) levels than those without this allele, particularly in subjects with ApoE varepsilon4 allele.
Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fator A de Crescimento do Endotélio Vascular/genética , Proteínas tau/líquido cefalorraquidiano , Idade de Início , Idoso , Doença de Alzheimer/metabolismo , Apolipoproteína E4/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo Genético , Regiões Promotoras Genéticas , TunísiaRESUMO
BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia. Currently, no definitive diagnostic test for AD exists. Cerebrospinal fluid (CSF) concentrations of amyloid beta (Abeta1-42) peptides and total tau proteins (T-tau) may serve as biomarkers for AD. AIM: The objective of this study was to investigate the usefulness of CSF Abeta1-42 and T-tau analyses in the diagnosis of AD with Tunisians. METHODS: We focused on three groups originating from Central Tunisian that matched in age (range 48-85): healthy controls (n = 53), AD patients (n = 93) and non-Alzheimer (nAD) dementia (n = 35) patients. Abeta1-42 and T-tau levels were measured in CSF by sandwich enzyme-linked immunosorbent assay. RESULTS: The ratio of T-tau/Abeta1-42 at baseline yielded a sensitivity of 85.3% for detection of AD and the specificity was 84.8% to differentiate controls and nAD dementia. CONCLUSION: Our findings confirm the use of T-tau/Abeta1-42 ratio in the discrimination of AD patients from all other patients.
