Genetic epidemiological study of maternal and paternal transmission of Alzheimer's disease.
Recent evidence for mitochondrial mutations associated with Alzheimers disease (AD) suggests the possibility of maternal transmission of this illness. We investigated this hypothesis by examining, in a variety of ways, the risk of a primary progressive dementia (PPD) in the parents (n = 650) and siblings (n = 1,220) of 325 AD probands. The results did not support maternal transmission in AD: The mothers of AD probands were not at greater risk of PPD than the fathers or the sisters of AD probands; the offspring of affected mothers were not at greater risk than the offspring of affected fathers or families with no affected parent; and, after selecting those proband families with evidence for increased familial loading, such families did not more frequently have affected mothers than fathers. In contrast, the cumulative 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 significantly higher than the offspring of no affected parents. While no evidence for maternal transmission in AD was observed, unexpectedly, we did find evidence of increased paternal transmission.
Ehrenkrantz
D
D
Department of Psychiatry, Mt. Sinai School of Medicine, New York, New York 10029, USA.
Silverman
J M
JM
Smith
C J
CJ
Birstein
S
S
Marin
D
D
Mohs
R C
RC
Davis
K L
KL
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D005220:Fathers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009035:Mothers; D012306:Risk