The tRNAGln 4336 mitochondrial DNA variant is not a high penetrance mutation which predisposes to dementia before the age of 75 years

Abstract

The genetic factors that predispose to Alz-heimer's disease (AD) are heterogeneous. Two recent reports have suggested that a niitochondrial DNA mutation within the tRNActe gene, located at position 4336, may be a risk factor for AD, as it was found in 10/256 (3.9%) cases with AD confirmed by necropsy. Although low prevalences of this mutation were detected in non-demented subjects in both of these studies, the con-trols were not carefully matched with the AD cases. We have investigated the fre-quency of this mutation in two community based elderly cohorts in Cambridgeshire, who have participated in longitudinal studies of cognitive function. The 4336 niitochondrial mutation was detected in 8/ 443 people examined. These people were found to be non-demented at ages 74, 81, 84, 86,89, 90, 91, and 102 years, in contrast to the previously described cases whose onset of dementia occurred between 60 and 76 years (mean 68). Accordingly, we believe that this niitochondrial variant is not a high penetrance mutation which pre-disposes to dementia before the age of 76 years.