Missing apolipoprotein E ε4 allele associated with nonamnestic Alzheimer's disease in a Tunisian population.

In this study, we investigate the impact of apolipoprotein E epsilon 4 (APOE ε4) as a major risk factor of Alzheimer's disease (AD), based on the clinical presentation of the disease in our population on the one hand, and comparison of the results with the findings from the literature on the other hand. Our study covered a population of 144 patients versus 90 healthy controls matched with each other in terms of age, gender, age of onset, etc. All patients underwent neurological examination, comprehensive neuropsychological assessment and brain magnetic resonance imaging. Controls were selected based on the neurological examination and the Arabic version of the minimental state examination (MMSE). Patients were classified as probable typical amnestic AD and atypical nonamnestic AD if the patient had logopenic variant primary aphasia, posterior cortical atrophy, behavioural or dysexecutive variants, corticobasal syndrome, nonfluent and semantic variants of primary progressive aphasia associated to biological diagnosis for AB42, Tau and Ptau biomarks in the cerebrospinal fluid. Genotyping was performed using the polymerace chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The study of the allelic frequency of APOE in cases and controls show that APOE ε4 is associated with an increased risk for AD (P = 0.002). We observed that the distribution of APOE ε4 within the AD group differs depending on the phenotype. Nonamnestic AD was more common in patients not carrying APOE ε4 (APOE ε4 (-)) compared to carriers of homozygous or heterozygous APOE ε4 (APOE ε4 (+)) (P = 0.038). In addition to its known effect as a major risk factor, we found that patients with AD are APOE ε4 negative, they show cognitive decline in nonmemory domains (language, behaviour, attention, executive and visuospatial functions).

Association between H2 haplotype of microtubule associated protein tau gene (deletion / insertion) with Alzheimer Disease in Tunisian patients.

It is widely recognized that Alzheimer's disease (AD) is the main cause of dementia in the elderly. AD is typically characterized by the extraneuronal plaque made up essentially of the amyloid ß peptide and intraneuronal tangles of hyperphosphorylated microtubule-associated Tau protein. This study investigates the possible interaction between AD and the deletion/insertion polymorphism in intron 9 of the Tau gene haplotype and APOE state in a Tunisian AD cases population (n = 85) and control (n = 91). The H2/H2 genotype was higher in the AD group as compared to the controls (22.4% vs. 7.8%). The frequency of H2 allele is higher in the patients group, and the difference of allele frequency is statistically significant between the two groups (χ2 = 12.220, p < 0.05). H2 allele is correlated with the female gender within the patient group (χ2 = 7.649, p = 0.006) Tau H2 haplotype can be identified as a risk factor of AD in the studied Tunisian population and was associated to female gender. There is no significant correlation between the frequency of Tau gene ins/del polymorphism and cognitive profile distribution in the patient group (p > 0.05).

Association between ACE polymorphism, cognitive phenotype and APOE E4 allele in a Tunisian population with Alzheimer disease.

Angiotensin-converting enzyme (ACE) has shown altered activity in patients with neurological diseases. An insertion/deletion (I/D) polymorphism of the ACE gene encoding angiotensin-converting enzyme has been reported to be associated with the risk for Alzheimer's disease (AD), and is generally considered to be a disorder primarily affecting memory. We conducted a case-control study in a sample composed of 85 sporadic AD patients and 90 age- and sex-matched controls to investigate the possible effect of the polymorphism and cognitive profile. Our data revealed an association between the ACE polymorphism and AD risk. There was a significant difference in the ACE allele or genotype frequencies between cases and controls. The D/D genotype showed an increased risk for AD and in the amnestic group and the effect was independent on ApoE genotypes.

Novel presenilin 1 mutation (p.I83T) in Tunisian family with early-onset Alzheimer's disease.

A minority of Alzheimer disease (AD) patients begin presenting symptoms before the age of 65 years. A familial aggregation is often found in this group of early-onset AD, and, in a subset of families, the pattern of inheritance is consistent with autosomal dominant inheritance. Fully penetrant variants in amyloid precursor protein, presenilin 1 (PSEN1), and presenilin 2 are the only causative mutations reported for autosomal dominant AD. This study is to explore the PSEN1 gene mutation in a Tunisian familial Alzheimer's disease. The patient in this family showed a novel missense mutation in exon 4 of the PSEN1 gene (complementary DNA 248T>C), altering isoleucine to threonine at 83 position. Because the change occurred in conserved domains of this gene, and cosegregated with affected family member, we suggested that this change may have a mutagenic and probably pathogenic effect.

Association between Alzheimer disease and the -491T allele of regulatory region polymorphism of Apolipoprotein E in a Tunisian population.

The apolipoprotein E (APOE) is a well-established risk factor for late-onset Alzheimer's disease (AD). Several studies have attempted to confirm the association between the polymorphism located at position -491 in the transcriptional regulatory region of the APOE gene and AD. We examined in 85 AD patients and 90 control subjects of a Tunisian population the potential involvement of this polymorphism as a risk factor for AD, either through an independent effect or through interaction with the existing APOE ε4 allele risk. The T allele frequency was significantly higher in the AD patients group (45.3 %) than in the controls group (32.78 %) and may possibly constitute a significant risk factor for AD. The APOE ε4 allele did not influence the distribution of the -491 polymorphism after stratification.