Differences in tau and apolipoprotein E polymorphism frequencies in sporadic frontotemporal lobar degeneration syndromes

Background: Frontotemporal lobar degeneration (FTLD) has different clinical phenotypes and is associated with several pathologic findings, most commonly dementia lacking distinctive histology or Pick disease. We know that the tau H1 haplotype is associated with some clinical and histologic phenotypes, for example, progressive supranuclear palsy and corticobasal degeneration. Furthermore, the apolipoprotein ε4 allele (APOE ε4) may be associated with Pick disease. Objective: To determine if different clinical phenotypes of FTLD are associated with different tau haplotype and APOE allele frequencies. Patients and Methods: All patients with FTLD with available DNA specimens (n = 63) seen at the Mayo Clinic, Jacksonville, Fla, were retrospectively classified according to the following clinical phenotypes: frontal dementia (FD); progressive, nonfluent aphasia (PA); or fluent, anomic aphasia (AA). DNA specimens were genotyped for APOE allele and tau haplotype frequencies and were compared with cognitively normal patients (n = 338) and patients with Alzheimer disease (AD) (n = 193). Results: Patients with AA had increased APOE ε4 frequency (30.4%) compared with patients with FD (14.8%, P = .04) and cognitively normal patients (11.1%, P<.001). Patients with AA also had increased tau H2 haplotype (37.0%) frequency compared with patients with FD (11.1%, P = .002), patients with AD (21.8%, P = .02), and cognitively normal patients (19.8%, P= .004). The increase in tau H2 haplotype frequency (50.0%) is especially pronounced in patients with AA who are APOE ε4 positive compared with patients with FD (18.8%, P = .04), patients with AD (24.8%, P = .005), and cognitively normal patients (15.3%, P<.001). APOE ε4 and tau H2 haplotype frequencies are not significantly different in patients with FD and PA compared with healthy patients. Conclusions: Clinical subtypes of FTLD have different tau and APOE genotype frequencies, suggesting these genes may influence the clinical presentation. Further studies should be performed to confirm this finding and to see if the pathologic phenotypes are also associated with different tau and APOE genotype frequencies.