Genetic epidemiological study of maternal and paternal transmission of Alzheimer's disease

Recent evidence for mitochondrial mutations associated with Alzheimers dise ase (AD) suggests the possibility of maternal transmission of this illness. We investigated this hypothesis by examining in a variety of ways, the ris k of a primary progressive dementia (PPD) in the parents (n = 650) and sibl ings (n = 1,220) of 325 AD probands. The results did not support maternal t ransmission in AD: The mothers of AD probands were not at greater risk of P PD than the fathers or the sisters of AD probands; the offspring of affecte d mothers were not at greater risk than the offspring of affected fathers o r families with no affected parent; and, after selecting those proband fami lies with evidence for increased familial loading such families did not mor e frequently have affected mothers than fathers. In contrast, the cumulativ e risk of PPD in fathers of AD probands, while similar to that of mothers, was significantly increased over the brothers of AD probands. In addition, the cumulative risk curve of PPD in the offspring of affected fathers was s ignificantly higher than the offspring of no affected parents. While no evi dence for maternal transmission in AD was observed, unexpectedly, we did fi nd evidence of increased paternal transmission. Am. J. Med. Genet. (Neurops ychiatr. Genet.) 88:378-382, 1999. (C) 1999 Wiley-Liss, Inc.