Folic acid is believed to play a role in protection from oxidant stress. Low levels of folic acid had been found in serum from patients with Alzheimer disease (AD). Folate concentration was evaluated in sera from 136 patients with cortical dementia [AD, n=108; frontotemporal dementia (FTD), n=28], 57 patients with subcortical dementia [Lewy body disease (LBD), n=9; corticobasal degeneration (CBD), n=5; progressive supranuclear palsy (PSP), n=6; Parkinson disease with dementia (PD-Dem), n=37], and 76 nondemented, healthy age-matched people. Serum folic acid levels were decreased in patients with AD and FTD as compared with either controls or patients with subcortical dementia (3.60+/-2.22 and 5.37+/-2.92 microg/L versus 6.87+/-3.50 microg/L, respectively; P<0.01). A tendency towards decreased folate concentration was found in LBD and CBD, but not to a significant extent. The highest proportion of folate-deficient patients was found in CBD, FTD and AD (respectively, 60, 48.2 and 46.3% versus 7.9% in controls; P<0.001). Folate deficiency characterizes FTD as well as AD. These differences observed among different clinical dementing syndromes may be related to neocortical damage.