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Science 5 March 1982:
Vol. 215. no. 4537, pp. 1243 - 1245
DOI: 10.1126/science.6120571

Articles

Science, Vol 215, Issue 4537, 1243-1245
Copyright © 1982 by American Association for the Advancement of Science


articles

Alzheimer's disease: insolubility of partially purified paired helical filaments in sodium dodecyl sulfate and urea

DJ Selkoe, Y Ihara, and FJ Salazar

A method is described for the partial purification of the paired helical filaments that accumulate progressively in human neurons in Alzheimer's disease (senile dementia). Paired helical filaments have unusual solubility characteristics, including insolubility in sodium dodecyl sulfate, urea, reducing agent, and guanidine, which prevent analysis of their molecular composition by gel electrophoresis. The paired helical filaments appear to contain covalent bonds other than disulfide, which cross-link individual filaments into a rigid intracellular polymer. Thus, paired helical filaments appear to represent an example in neurons of an insoluble cross-linked protein. Covalently cross-linked protein polymers occur in lens senile cataracts and in terminally differentiated skin keratinocytes, suggesting that there may be a common mechanism for remodeling some structural proteins during cell aging.


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