Apolipoprotein E Â4 Allele Is a Risk Factor for Alzheimer’s Disease: The Central Region of Portugal (Coimbra) as a Case Study

Alzheimer’s disease (AD), an age-associated neurodegenerative disorder, is characterized by a progressive decline of the cognitive functions, in particular a loss of memory, learning and attention, and it does not have a simple etiology. Most of the cases are sporadic and the factors involved are unknown. A very small percentage of cases are hereditary and are due to mutations in one of the three genes: amyloid precursor protein (APP) on chromosome 21, presenilin-1 (PS1) on chromosome 14 or presenilin-2 (PS2) on chromosome 1. A fourth gene on chromosome 19 encoding the protein apolipoprotein E (Apo E) also appears to be implicated in the disease [1]. The Apo E gene is polymorphic with three major alleles – Â2, Â3, and Â4 – and results in six genotypes – Â2/Â2, Â2/Â3, Â3/Â3, Â3/Â4, Â4/Â4, and Â2/Â4. The Â3 allele is the most common in the general population. The Â4 allele increases the risk of AD and lowers the age of onset in a dosedependent manner. Conversely, Â2 allele decreases the risk and delays AD onset [1]. In the present study we examined the Apo E genotype and allele frequencies as well as the relative risk of dementia in probable AD patients and control subjects of the central region of Portugal (Coimbra). Seventy-four probable AD patients, 42 female and 32 male (age range 41–85 years; mean 68.243 B 9.017 years) were recruited from the Neurological Unit of the University Hospital of Coimbra. Thirtyfive age-matched healthy subjects free of cognitive impairment, 18 female and 17 male (age range 47–84 years; mean 64.971 B 10.416 years) were recruited from the informants (spouses or nonkindred) for the cases with whom they share similar age and socioeconomic Table 1. Apo E genotypes distribution and allele frequencies