APOE GENOTYPES IN AUSTRALIA - ROLES IN EARLY AND LATE-ONSET ALZHEIMERS-DISEASE AND DOWNS-SYNDROME

WE studied the apoE genotypes of 279 Australians in order to determine what relationships might exist in this group between apoE genotype and dementia associated with either early- or late-onset sporadic Alzheimer's disease (AD) or with Down)s syndrome (DS). ApoE epsilon 4 allele frequency was increased in Australians with either early-onset sporadic AD (p<0.002) or late-onset sporadic AD (p<0.0001) and apoE epsilon 2 allele frequency was decreased in the late-onset sporadic AD group (p<0.01). The apoE genotype distribution among patients with DS was not different from that of the control group. One individual with DS and an apoE epsilon 4/epsilon 4 genotype developed dementia at the earliest age of dementing DS patients, consistent with a role for apoE epsilon 4 in determining age of onset of dementia in AD and DS. Another DS patient with an apoE epsilon 2/epsilon 3 genotype developed dementia within an age range similar to that of four demented DS patients with an apoE epsilon 3/epsilon 3 genotype, an observation which would appear inconsistent with the proposed protective effect of apoE epsilon 2 to delay onset of dementia in DS. These results extend the evidence that the apoE genotype, particularly apoE epsilon 4, modulates dementia in early- and late-onset sporadic AD and DS. The protective role of apoE epsilon 2 in DS, however, may vary among different populations or ethnic groups.