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June 1991

Association of Decreased Paternal Age and Late-Onset Alzheimer's Disease: An Example of Genetic Imprinting?

Author Affiliations

From the Department of Neurology, School of Medicine (Drs Farrer and Wolf), and the School of Public Health (Drs Farrer and Cupples), Boston (Mass) University; Department of Neurology, Harvard Medical School (Drs Farrer and Growdon and Ms Connor); and the Section of Preventive Medicine and Epidemiology, Department of Medicine, University Hospital (Dr Wolf), Boston.

Arch Neurol. 1991;48(6):599-604. doi:10.1001/archneur.1991.00530180051017

• 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.