Frequency of tau mutations in three series of non-Alzheimer's degenerativedementia

Splice-site and missense mutations have been identified in tau associated w ith frontotemporal dementia with parkinsonism linked to chromosome 17. In t his study we assessed the genetic contribution of tau mutations to three pa tient series with non-Alzheimer's (non-AD) degenerative dementia. The group s included (1) a community-based dementia series from Minnesota, MN; (2) a referral series with clinicopathological tauopathy; and (3) a pathologicall y confirmed familial frontotemporal dementia series from Manchester, UK. Co mparing the three clinical series: in the stringently diagnosed Manchester frontotemporal dementia series, tau mutations were present in 13.6% of case s (three splice-site mutations); in the clinicopathological referral series that used more general inclusion criteria, 3 cases with P301L mutations we re observed, which represents a lower mutation frequency of 3.6% (9.4% in f amilial cases); in contrast, tau mutations were not detected in the Minneso ta community-based dementia series, suggesting the occurrence of these muta tions in dementia generally is rare (<0.2%). These data identify the preval ence of mutations in three different clinical settings and indicate that th is figure is sensitive to the diagnostic criteria used in each patient seri es.