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.