Alzheimer's Disease/ Senile Dementia of the Alzheimer's Type

In the brain of patients with Alzheimer disease the nerve cells accumulate mass of aberrant filaments, the paired helical filaments (PHF). The number of these fibril accumulations. the neur ofibrillary tangles correlate strongly with the degree of dementia in the affected patients. Microtubule associated protein tau which stimulates microtubule assembly and maintain polymerized microtubules is one of the major components of PHF. Tau in PHF is abnormally phosphorylated. A novel tau peptide has been identified by amino acid sequencing. This peptide is also present in PHF. The access of tau peptide antibodies to PHF requires dephosphorylation of PHF confirming that tau in PHF is abnormally phosphorylated. The presence of abnormally phosphorylated tau is observed both in neurons with tangles and in some neurons where tangles are not detectable with silverstains. These studies suggest that tau in PHF is abnormally phosphorylated and that the accumulation of abnormally phosphorylated tau in the affected neurons precede the formation of the tangles. Studies on the site and nature of the abnormal phosphorylation of tau which will help elucidate the pathogenesis of Alzheimer disease are presently underway