Presence of tau in isolated nuclei from human brain.
Previous studies have demonstrated that the microtubule-associated protein (MAP) tau is present in the axonal and somatodendritic compartment of neurons. In cultured primate cell lines, tau has been found localized to the NOR regions of the acrocentric chromosomes in mitotic cells 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 against tau, Tau-1, Tau 46.1, and 5E2, we have established by both indirect immunofluorescence and Western blotting that tau is an integral component of nuclei isolated from Alzheimer's disease (AD) and pathologically normal control brains. Brain nuclear tau, like nuclear tau in primate cells, is insoluble in SDS and must first be extracted with formic acid prior to analysis by Western blot. Immunoblot analysis of isolated brain nuclei displays the characteristic ladder of tau proteins and demonstrates that all isoforms of tau are present. It is unclear whether levels of nuclear tau can be correlated to pathologic events in AD, but its insoluble nature along with reports of intranuclear PHFs warrant further studies of nuclear tau as a molecular candidate in the genesis of AD.
Brady
R M
RM
Molecular Geriatrics Corporation, Lake Bluff, IL 60044, USA.
Zinkowski
R P
RP
Binder
L I
LI
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D016875:tau Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016875:tau Proteins