BRAIN LEVELS OF MICROTUBULE-ASSOCIATED PROTEIN-TAU ARE ELEVATED IN ALZHEIMERS-DISEASE - A RADIOIMMUNO-SLOT-BLOT ASSAY FOR NANOGRAMS OF THE PROTEIN

The microtubule-associated protein-tau, which stimulates the assembly of alpha-beta tubulin heterodimers into microtubules, is abnormally phosphorylated in Alzheimer's disease (AD) brain and is the major component of paired helical filaments. In the present study, the levels of tau and abnormally phosphorylated-tau were determined in brain homogenates of AD and age-matched control cases. A radioimmuno-slot-blot assay was developed. using a primary monoclonal antibody, Tau-1. and a secondary antibody, anti-mouse I-125-immunoglobulin G. To assay the abnormally phosphorylated-tau, the blots were treated with alkaline phosphatase before immunolabeling. The levels of total-tau were about eightfold higher in AD (7.3 +/- 2.7 ng/mu-g of protein) than in control cases (0.9 +/- 0.2 ng/mu-g), and this increase was in the form of the abnormally phosphorylated protein. These studies indicate that the abnormal phosphorylation-not a decrease in the level of tau-is a likely cause of neurofibrillary degeneration in AD.