THE MICROTUBULE PROTEIN TAU IN ALZHEIMER'S DISEASE

之前，我们已经证明了一个异常磷酸化

Previously, we have shown that an abnormally phosphorylated form of the microtubule-associated protein, tau is intimately associated with paired-helical filaments and is overexpressed in Alzheimer brain. Using our knowledge of the basic biology of this protein, we propose to compare the biochemistry and cell biology of soluble tau from Alzheimer brain with that from non-demented control brain. To determine whether disease related alterations affect tau's purported "normal" function, purified tau from Alzheimer and control brains will be assayed for its efficacy in stimulating microtubule assembly in vitro. Furthermore, with two existing monoclonal antibodies to tau, one which does not bind to the abnormally phosphorylated form and one which binds to all forms of this protein, we propose to: 1) determine the amounts of soluble tau in Alzheimer vs. non-demented brains, 2) correlate the number of tau-containing senile plaques and neurofibrillary tangles as determined by immunohistochemistry with the levels of soluble tau in tissue extracts, 3) determine the amount of tau in CSF and serum form patients with Alzheimer disease vs. non- demented control populations, 4) determine the ratio of phosphorylated/nonphosphorylated tau in brain tissue extracts, sera and CSF of Alzheimer vs. control samples, and 5) to supply these data to the Core for correlation with diagnostically determined degrees of dementia. In addition, novel monoclonal antibodies will be raised which bind to Alzheimer tau but not to normal tau in order to obtain probes which target phosphorylation and other possible alterations in this protein as a part of Alzheimer pathology.