Paternal age is a risk factor for Alzheimer disease in the absence of a major gene

Paternal age is a risk factor for Alzheimer disease in the absence of a major gene
Journal neurogenetics
Publisher Springer Berlin / Heidelberg
ISSN 1364-6745 (Print) 1364-6753 (Online)
Issue Volume 1, Number 4 / August, 1998
Category Original article
DOI 10.1007/s100480050041
Pages 277-280
Subject Collection Biomedical and Life Sciences
SpringerLink Date Monday, August 17, 1998
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Original article
Paternal age is a risk factor for Alzheimer disease in the absence of a major gene
L. Bertram1, R. Busch2, M. Spiegl1, N. T. Lautenschlager1, U. Müller3 and A. Kurz1

(1) Department of Psychiatry, Technical University Munich, Möhlstrasse 26, D-81675 Munich, Germany, DE
(2) Department of Medical Statistics and Epidemiology, Technical University, Munich, Germany, DE
(3) Department of Human Genetics, Justus-Liebig University, Giessen, Germany, DE

ABSTRACT We compared the parental age at birth of patients with Alzheimer disease (AD) with that of cognitively healthy control subjects. Within 206 carefully diagnosed AD patients, two groups were distinguished according to the likelihood of carrying a major gene for AD (MGAD). This likelihood was calculated by applying a Bayesian approach which incorporates data on aggregation of the disease, age at onset, and "censoring" ages within the family. All AD patients were ranked by MGAD probability. According to the sample's quartiles, two subgroups were defined representing the 52 individuals with the lowest and the 52 with the highest MGAD probability. Age at onset of dementia, education, and apolipoprotein E ε  4 allele frequencies were not statistically different between the two groups. Fathers of patients with a low MGAD probability were significantly older (35.7±8.1 years) than fathers of both other groups (high MGAD probability 31.3±6.9 years, P =0.004; controls 32.6±6.8 years, P =0.04, n=50). The differences for mothers were less pronounced and not statistically significant. These findings suggest that increased paternal age is a risk factor for AD in the absence of a major gene, whereas increased maternal age and AD are associated only weakly and independently of genetic disposition.
Key words Alzheimer disease - Risk factors - Parental age - Genetics

Received: February 23, 1998 / Revised and Accepted: May 20, 1998

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