Association of decreased paternal age and late-onset Alzheimer's disease. An example of genetic imprinting?
L. A. Farrer, L. A. Cupples, L. Connor, P. A. Wolf and J. H. Growdon
Department of Neurology, Boston University School of Medicine, MA 02118.
Several studies have identified advanced maternal age as a risk factor for
Alzheimer's disease. This study evaluated maternal and paternal age at
birth of 237 patients with Alzheimer's disease, each of whom was matched to
five control subjects based on sex, year of birth, survival age, and
location of residence. It was found that decreased paternal age
substantially increased the susceptibility to the common form of
Alzheimer's disease that occurs after the age of 67 years, whereas advanced
maternal age had a negligible effect on risk of Alzheimer's disease. The
higher incidence of late-onset Alzheimer's disease among persons born to
younger fathers is consistent with a genetic imprinting mechanism involving
DNA methylation. The proposed model postulates a role for environmental
agents in the pathogenesis of Alzheimer's disease and accounts for families
that show an aggregation of cases but no apparent pattern of inheritance.
