Folate and homocysteine in the cerebrospinal fluid of patients with Alzheimer's disease or dementia: a case control study.

BACKGROUND: Amyloid deposition in the brain is an early event in Alzheimer's disease (AD), but a dysfunction of the blood-brain barrier or a disturbance in the metabolism of folate and homocysteine (Hcy) may affect the development of dementia. We investigated if the concentrations of folate and Hcy would be modified in cerebrospinal fluid (CSF) of clinically diagnosed AD patients. METHODS: We included 70 AD patients, 33 patients with another type of dementia (nAD) and 30 age-matched control subjects. Plasma Hcy was assayed as well as Hcy, folate, Aß1-42 and T-tau in CSF. We used ANOVAs for comparison between groups, and then pairwise comparisons by Wilcoxon tests with Bonferroni-corrected p values. Correlations were tested with the Spearman's rank test. RESULTS: Levels of Aß1-42, T-tau and folates in CSF were significantly different between groups, but not Hcy. In addition, the average folate in CSF was lower in AD patients compared with controls (18.7 ± 2.4 vs. 20.3 ± 1.7 nmol/l, Bonferroni-corrected p value < 0.02). There was no correlation between Aß1-42 or T-tau and folate or Hcy in CSF, regardless of the group. In the AD group, there was a significant inverse correlation between Hcy and folate in CSF (ρ = -0.63, p < 0.0001), whereas in the nAD group, a significant correlation was found for Hcy between plasma and CSF (ρ = 0.59, p < 0.0005). CONCLUSION: The concentration of folate in CSF was found to be decreased in AD patients. These findings support the hypothesis of a possible role of folate in the onset or worsening of AD.

Polymorphism in apoA1 Influences High-Density Lipoprotein Cholesterol Levels but Is Not a Major Risk Factor of Alzheimer's Disease.

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.

Analysis of association between bleomycin hydrolase and apolipoprotein E polymorphism in Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia. Several studies indicate a possible relationship between different genes and Alzheimer's disease. To further investigate, we have analyzed the association between the bleomycin hydrolase (BLMH) and apolipoprotein E (ApoE) polymorphisms in 93 AD patients and age- and sex-matched 113 controls from the Tunisian population. The frequency of ApoE epsilon 4 allele was found to differ significantly in AD patients compared to the control [29.5% vs. 8.8 (χ (2) = 26, df = 1, p < 0.001)] leading to an increased risk of AD in subjects with this allele (OR = 3.29, 95% CI = 1.7-6.5; p = 0.001]. This risk was found to decrease from OR = 8.4, CI = 3.3-23; p < 0.001 in subjects less than 75 years old to OR = 1.2, CI = 1.031-14; p = 0.0297 in subjects 75 years and older. No association was observed between carrying the BLMH-G genotype and AD in ε4 negative or positive subjects.

-1154G/A and -2578C/A polymorphisms of the vascular endothelial growth factor gene in Tunisian Alzheimer patients in relation to beta-amyloid (1-42) and total tau protein.

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.

Evaluation of cerebrospinal fluid tau/beta-amyloid(42) ratio as diagnostic markers for Alzheimer disease.

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.

CSF beta-amyloid 1-42 and tau in Tunisian patients with Alzheimer's disease: the effect of APOE epsilon4 allele.

Alzheimer's disease (AD) is the leading cause of dementia. Currently, no definitive diagnostic test for AD exists. An accurate, convenient and objective test to detect AD is urgently needed for efficient drug development and effective clinical use of emerging therapies. The aim of the present work is to investigate the usefulness of cerebrospinal fluid (CSF) beta-amyloid protein (Abeta1-42) and total tau protein (t-tau) analyses in the diagnosis of AD and whether apolipoprotein E (ApoE) epsilon4 allele is a factor for AD affecting Tunisian people. Abeta1-42 and t-tau levels were measured in CSF from AD patients (n=73), non-Alzheimer dementia (nAD, n=35) and healthy controls (HC, n=38) by sandwich enzyme-linked immunosorbent assay. Abeta1-42 levels were decreased and t-tau increased in AD patients. The combination of Abeta1-42 and t-tau at baseline yielded a sensitivity of 87.4% for detection of AD. The specificities were 97.3% for controls and 82.7% for other dementia. The ApoE epsilon4 allele frequency (29.5%) was significantly higher in the AD patients than in the nAD patients (17.1%) or in the control groups (9.5%). AD patients carrying ApoE epsilon4 allele had lower Abeta1-42 (p<0.001) levels than those without a epsilon4 allele. The combination of t-tau and Abeta1-42 is a robust and reliable assay that may be useful in discriminating cases at risk for AD such as ApoE epsilon4 allele carriers from nAD patients or from age-matched control subjects.