Previous studies have demonstrated that the microtubule-associated pro
tein (MAP) tau is present in the axonal and somatodendritic compartmen
t of neurons. In cultured primate cell lines, tau has been found local
ized to the NOR regions of the acrocentric chromosomes in mitotic cell
s and the dense fibrillar regions of nucleoli in interphase cells. We
report here the presence of nuclear tau in nuclei isolated from fresh,
frozen human frontal cortex. Using several monoclonal antibodies agai
nst tau, Tau-l, Tau 46.1, and 5E2, we have established by both indirec
t immunofluorescence and Western blotting that tau is an integral comp
onent of nuclei isolated from Alzheimer's disease (AD) and pathologica
lly normal control brains. Brain nuclear tan, like nuclear tau in prim
ate cells, is insoluble in SDS and must first be extracted with formic
acid prior to analysis by Western blot. Immunoblot analysis of isolat
ed brain nuclei displays the characteristic ladder of tau proteins and
demonstrates that all isoforms of tau are present. It is unclear whet
her levels of nuclear tau can be correlated to pathologic events in AD
, but its insoluble nature along with reports of intranuclear PHFs war
rant further studies of nuclear tau as a molecular candidate in the ge
nesis of AD.