Clinic-based cases with frontotemporal dementia show increased cerebrospinal fluid tau and high apolipoprotein E epsilon 4 frequency, but no tau genemutations

Frontotemporal dementia (FTD) belongs to a group of neurodegenerative disor ders known as tauopathies, characterized by intracellular aggregation of hy perphosphorylated tau protein in the brain. Some tauopathies, like Alzheime r's disease (AD), consistently show increased levels of tau protein in cere brospinal fluid (CSF), However, similar studies in FTD populations have sho wn variable results, although mutations in the tau gene are identified as c auses of disease in certain FTD families. In the present study, a Swedish c linic-based FTD population was investigated with respect to CSF tan levels, apolipoprotein E (APOE) genotype distribution and occurrence of mutations in the tau gene. CSF tau levels were significantly increased among FTD pati ents (534 +/- 235 pg tau/ml, P < 0.001) (n = 47) compared to controls (316 <plus/minus> 137 pg tau/ml) (n = 51), Furthermore, a strong increase in the APOE epsilon4 allele frequency was found in the FTD population, as 52% wer e epsilon4 carriers, compared to 21% of the controls. However, no mutations in the tau gene were identified. These findings support the present notion of a common pathogenic pathway in the disease processes for several tauopa thies, with both APOE epsilon4 and CSF tau being a pathological link betwee n the different disorders. Furthermore, we conclude that mutations in the t au gene are a rare cause of FTD, (C) 2001 Academic Press.