The microtubule-associated proteins (MAPs), tau and MAP1B are highly regulated during normal neuronal development. Evidence is accumulating suggesting the re-emergence of fetal characteristics in vulnerable neurons involved in Alzheimer's Disease (AD) pathology. Both fetal and adult forms of tau are known to be integral components of the paired helical filament (PHF) and preliminary evidence indicates that Ad-affected neurons express high levels of MAP1B. Therefore, we propose to determine the relative amounts of both of these proteins in brain regions and to determine the fetal/adult tau ratios in AD and control brains. Studies will continue to asses the properties of AD vs control tau and the AD protein, A68. Non- tubulin tau interacting proteins (TIPs), and a newly described 200 kDa tau- like polypeptide will be and quantified in AD and control brain. Microtubule binding studies will be performed using AD and normal soluble tau as well as A68 to ascertain whether these properties are altered in the disease state. In addition, the ability of the AD neuron to metabolize altered tau will be assessed by in vitro protease experiments and the amounts of tau in AD and control CSFs will be determined. Successful completion of these experiments will aid in establishing the degree to which tau, MAP1B and the 200 kDa polypeptide are altered in either their expression, form or interactions in AD pathology.
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