Measurement of distinct immunochemical presentations of tau protein in Alzheimer disease.
The tau protein is a microtubule-associated protein that is normally located in nerve axons. In Alzheimer disease, it is a constituent of paired helical filaments (PHFs), which are the principal fibrous component of the characteristic neurofibrillary tangles. The tau protein, therefore, is abnormally sequestered in an insoluble form in PHFs in the cell body and dendrites in Alzheimer disease. We have used two monoclonal antibodies (mAbs) to selectively measure the levels of normal, soluble tau protein and of PHF-associated tau protein in the brain. mAb 423 binds to PHFs and recognizes a 12-kDa fragment of tau protein released by formic acid treatment of PHFs, but it does not recognize normal tau protein. In contrast, mAb 7.51 recognizes normal tau protein as well as the PHF core-derived tau fragment, but its epitope is concealed in the PHF-bound form. The differential binding properties for these two mAbs have enabled us in this study to quantify insoluble PHF-associated tau protein in the somatodendritic compartment as well as normal soluble tau protein in its predominantly axonal location. Our findings demonstrate that a distinct immunochemical presentation of tau protein recognized by mAb 423, a PHF-specific marker, can be used to quantify neurofibrillary pathology in Alzheimer disease independently of the presence of normal tau proteins.
Harrington
C R
CR
Cambridge Brain Bank Laboratory, University of Cambridge Department of Psychiatry, United Kingdom.
Mukaetova-Ladinska
E B
EB
Hills
R
R
Edwards
P C
PC
Montejo de Garcini
E
E
Novak
M
M
Wischik
C M
CM
D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D001921:Brain / Q000276:immunology; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure; D008870:Microtubules / Q000276:immunology; D009454:Neurofibrils / Q000276:immunology*; D012995:Solubility; D016875:tau Proteins
D000911:Antibodies, Monoclonal; D008869:Microtubule-Associated Proteins; D016875:tau Proteins