IMMUNO-CYTOCHEMICAL STUDIES OF NEUROFIBRILLARY TANGLES

  • 1 January 1981
    • journal article
    • research article
    • Vol. 104  (1) , 77-89
Abstract
The molecular nature of neurofibrillary tangles of senile dementia of the Alzheimer type (SDAT) was studied by immunoperoxidase and immunofluorescence techniques. Five antisera, including anti-human-brain-2-cycle-purified-microtubule-fractions (2 .times. MT), anti-calf-brain .times. MT, anti-sea-urchin-egg-tubulin, anti-beef-brain-tubulin and anti-human-brain-neurofilament(NF)-210 kilodalton-protein were tested for their binding to neurofibrillary tangles. The anti-human-2 .times. MT serum stained structures resembling neurofibrillary tangles, neurites of neuritic plaques, and microglia-like cells in SDAT brains, but no such staining pattern was detected in normal brain sections. In neurons isolated from SDAT brains, .apprx. 40% of the tangles were labeled by the anti-human-2 .apprx. MT serum with an identical pattern. Other antisera tested did not preferentially bind tangle-like structures in tissue sections and bound to 5% of the tangles in isolated neurons. Thus, the antigenic sites of tubulin and NF proteins are not shared by neurofibrillary tangles. Unlike the calf preparation, the human-2 .times. MT fractions contained a prominent protein band that was identical to ferritin in MW and cross-reacted with anti-human-2 .times. MT and anti-human-ferritin sera. Antisera to this ferritin-like protein, or anti-ferritin, did not stain neurofibrillary tangles. Although the calf 2 .times. MT and 2 other human MT fractions failed to elicit an antiserum that stained tangles, these fractions were able to remove the anti-human-2 .times. MT serum activity that binds to tangles. Evidently, the protein(s) that makes up neurofibrillary tangles of SDAT is present in various quantities in microtubule fractions of normal brain.