The long term objective of this project is to learn the etiology and the pathogenesis of Alzheimer disease and senile dementia of the Alzheimer type (AD/SDAT), a major public health problem in modern society with its rapidly increasing elderly population. The most characteristic lesion in AD/SDAT is the presence of numerous intraneuronal argentophilic fibrillary tangles which are composed of paired helical filaments (PHF). PHF are morphologically unlike any of the normal neurofibers, their origin is as yet not understood. The concentration of Alzheimer neurofibrillary tangles (ANT) strongly correlates to the degree of dementia. Although PHF of the Alzheimer type are not seen in normal young humans or aged animals, ANT/PHF cross-reacting antigens (ANTCA) are present both in normal young human and animal brain. In order to elucidate the role of ANTCA in the pathogenesis of Alzehimer neurofibrillary changes studies will be undertaken to l) biochemically isolate ANTCA polypeptide/s to homogeneity, raise polyclonal antibodies to it, study its localization by immunocytochemistry directly and by absorption of the ANT-staining antibodies with various subcellular fractions, 2)determine its levels by immunoassay in young, adult, aged and Alzheimer brain, and 3) biochemically characterize it in comparison with PHF polypeptides and normal neurofibrous proteins with respect to molecular weight, isoelectric point, amino acid analysis, peptide maps, and end group analysis. Establishment of the identity of ANTCA, its localization in brain and its comparison with PHF polypeptide/s might provide insight as to what determines the formation of ANT/PHF in the affected brain and what is the role of PHF in the pathogenesis of AD/SDAT.
Showing the most recent 10 out of 91 publications
