Summary
Antisera to microtubule-enriched fraction fron normal human brain (anti-MT sera) label neurofibrillary tangles and neurites of neuritic (senile) plaques in brain sections of cases with Alzheimer disease/senile demintia of the Alzheimer type (AD/SDAT); the plaque core amyloid is not labeled. These anti-MT sera label both tangles in tissue sections and smears of isolated tangles which had been extracted with sodium dodecyl sulfate (SDS) to remove impurities trapped in between the paired helical filaments (PHF). The tangle labeling of anti-MT sera is eliminated on their absorption both with microtubule-enriched fractions from human and animal brain and with the isolated PHF. Neurofilament triplet, actin, myosin, keratin, or fibroblasts do not absorb the tangles staining antibodies. Furthermore, antisera containing antibodies to tubulin, microtubule-associated high mol. wt. polypeptides (MAPS), neurofilament triplet, and the 50,000 mol. wt. contaminant of CNS neurofilament preparations do not label tangles. On immunoblots of SDS-polyacrylamide gels of isolated PHF anti-MT sera label some of the same polypeptides identified with antisera to PHF; affinity-purified antibodies to tubulin used as a control do not label any PHF polypeptide on the immunoblots. The anti-MT sera, when preabsorbed with the PHF polypeptides eluted from SDS-polyacrylamide gels, do not label tangles. These studies demonstrate that a polypeptide/s cross-reactive with Alzheimer PHF is indeed normally present in brain and that it is different from tubulin, neurofilament triplet, actin, myosin, vimentin, and keratin.
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Parts of this paper were reported at the XIIth International Congress of Gerontology, Satellite Symposium, Heidelberg, Federal Republic of Germany, 1981; at the IXth International Congress of Neuropathology, Vienna, Austria, 1982; and at the 60th Annual Meeting of the American Association of Neuropathologists, San Diego, CA, USA, 1984
Supported by NIH grants NS 18105 and NS 17487
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Grundke-Iqbal, I., Iqbal, K., Tung, Y.C. et al. Alzheimer paired helical filaments: Cross-reacting polypeptide/s normally present in brain. Acta Neuropathol 66, 52–61 (1985). https://doi.org/10.1007/BF00698295
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DOI: https://doi.org/10.1007/BF00698295