[Frequency of the APOE-4 allele in Alzheimer's disease and its variation with age in Asturias (Spain)]. / Frecuencia del alelo APOE-4 en la enfermedad de Alzheimer en la población asturiana y su variación con la edad.

BACKGROUND: Patients with late-onset Alzheimer's disease show a higher frequency of the APOE-4 than controls. The usefulness of the APOE genotyping in the diagnosis of the disease is controversial. Recently, an age dependent prevalence of APOE-4 in Alzheimer's disease has been described, with a maximum frequency for patients with an age at onset between 65 and 80 years. Additionally, the APOE-4 frequency in healthy controls is similar among the different age-groups, including healthy octogenarians. These data suggest that APOE-4 determines when and not who will develop the disease. PATIENTS AND METHODS: The APOE genotype was defined following a previously described PCR-protocol. We analysed 120 patients with clinically defined probable Alzheimer's disease and 250 controls from the same Caucasian population (Austrias, Northern Spain). RESULTS: We found a significantly higher frequency of the APOE-4 in patients, compared to controls (p = 0.00001). The prevalence of this allele was 65% among patients with an age at onset 66-70, falling to 36% and 18% in patients younger than 65 and older than 80 years, respectively. The average age (SD) at onset did not differ between the E-44 (69 years), E-34 (73 years) and E-33 (73 years). APOE-4 frequency was similar between the different age-groups of controls, including healthy octogenarians. CONCLUSIONS: In Asturias, APOE genotyping can not be used for the presimptomatic diagnosis of Alzheimer's disease. However, individuals carrying this allele would have a higher probability of developing the disease at an age between 65 and 80 years if they are predisposed (genetically and/or environmentally) to the disease.

Angiotensin converting enzyme and endothelial nitric oxide synthase DNA polymorphisms and late onset Alzheimer's disease.

OBJECTIVES: Several lines of evidence suggest that the endothelial constitutive nitric oxide synthase (ecNOS) and angiotensin converting enzyme (ACE) may have a role in Alzheimer's disease. ACE is widely expressed in the brain, and a DNA polymorphism at the ACE gene has been linked to the risk for late onset Alzheimer's disease. Nitric oxide (NO) production by microglial cells, astrocytes, and brain microvessels is enhanced in patients with Alzheimer's disease. There is a growing evidence that NO is involved in neuronal death in Alzheimer's disease, and the oxidative stress caused by NO in the brain could be a pathogenic mechanism in Alzheimer's disease. The objective was to determine if two DNA polymorphisms at the ecNOS and ACE genes that have been linked with different levels of enzyme expression, have some effect on the risk of developing late onset Alzheimer disease. METHODS: A total of 400 healthy controls younger than 65 years and 350 patients with Alzheimer's disease (average age 72 years) were genotyped for the ACE and ecNOS polymorphisms. To define a possible role for these polymorphisms in longevity 117 healthy controls older than 85 years were also analysed. Genomic DNA was obtained and amplified by polymerase chain reaction, and genotypes were defined following a previously described procedure. Gene and genotype frequencies between patients and controls were compared statistically. RESULTS: Gene and genotype frequencies for the ecNOS and ACE polymorphisms did not differ between both groups of healthy controls (<65 years and >85 years). EcNOS gene and genotype frequencies were similar between patients and controls. There was a slight but significantly increased frequency of the ACE-I allele among patients with Alzheimer's disease compared with controls (p=0.03; OR=1.28, 95%CI= 1.04;1.58). CONCLUSIONS: The ACE-I allele was associated with a slightly increased risk of developing late onset Alzheimer's disease.

Association between an alpha(2) macroglobulin DNA polymorphism and late-onset Alzheimer's disease.

An association between a five-base-pair deletion/insertion DNA polymorphism at the alpha(2) macroglobulin gene (A2M) and late-onset Alzheimer's disease (LOAD) has been recently described. We developed a PCR assay to analyze this polymorphism in 190 LOAD patients (older than 65 years) and 400 controls from Spain. Controls were stratified into three groups: <65 years (n = 200), 65 to 80 years (n = 100), and 81 years or older (n = 100). We found a significantly higher frequency of carriers of the D allele in patients older than 81 years compared to controls older than 81 years (p = 0.0012). In addition, the frequency of the D allele was significantly lower in controls older than 81 years compared to controls younger than 65 (p = 0.048). Our work suggests that the D allele confers an age-dependent increased risk to develop late-onset Alzheimer's disease.

[Prognostic factors in multiple sclerosis in a population-based series in Asturias]. / Factores pronósticos de la esclerosis múltiple en una serie de base poblacional de Asturias.

We sought clinical, paraclinical and genetic (HLA) factors that might have prognostic value in predicting disability produced by multiple sclerosis. An epidemiologically based sample including 146 cases (86% remittent and 14% mainly progressive) was studied. The progression of disability was measured on an index after systematic follow-up of at least 3 years. Our results show that the prognosis is significantly worse for those with a high frequency of attacks (p < 0.001), multiple clinical signs at presentation (p < 0.05) or motor weakness. The best prognosis was associated with those whose symptoms began with sensory alterations (p < 0.05). Late onset correlated significantly with a short interval between the first and second attack (r = 0.24), and this short interval was in turn significantly correlated with higher frequency of attacks in later stages (r = 0.44). We conclude that cases with a short interval between the first two attacks and those with late onset have a poorer prognosis. The following variables also tended to be associated with a more unfavorable prognosis, although the relationship was not statistically significant: female, progressive form, an increase in gammaglobulins in spinal fluid, infratentorial lesions as evidenced by magnetic resonance, and the alleles HLA-DR4, DR7 and DQw8. The allele DQw5 tended to be associated with a better prognosis.