S. Sorbi et al., EPISTATIC EFFECT OF APP717 MUTATION AND APOLIPOPROTEIN-E GENOTYPE IN FAMILIAL ALZHEIMERS-DISEASE, Annals of neurology, 38(1), 1995, pp. 124-127
We found a new familial Alzheimer's disease kindred in which the disea
se cosegregates with the APP717Val-->Ile mutation and in which all of
the three most common apolipoprotein E (ApoE) alleles are represented.
We studied the relationship between ApoE genotype and the clinical ex
pression of the disease and found that in this amyloid precursor prote
in-mutated family, ApoE genotype influences the age at onset of the di
sease. Three mutated subjects heterozygous for the epsilon 4 allele ha
d the earliest age at onset in this family, subjects heterozygous for
the epsilon 2 allele had the latest age at onset, and subjects homozyg
ous for the epsilon 3 allele had an intermediate age at onset. In this
large kindred we also found an amyloid precursor protein-mutated subj
ect 2.4 standard deviations older than the mean age at onset without c
linical signs and symptoms of the disease and carrying the epsilon 2/e
psilon 3 genotype.