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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.<\/jats:p>","DOI":"10.1126\/science.6120571","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T18:30:32Z","timestamp":1160073032000},"page":"1243-1245","source":"Crossref","is-referenced-by-count":315,"title":["Alzheimer's Disease: Insolubility of Partially Purified Paired Helical Filaments in Sodium Dodecyl Sulfate and Urea"],"prefix":"10.1126","volume":"215","author":[{"given":"Dennis J.","family":"Selkoe","sequence":"first","affiliation":[{"name":"Ralph Lowell Laboratories, Mailman Research Center, McLean Hospital, and Department of Neurology, Harvard Medical School, Belmont, Massachusetts 02178"}]},{"given":"Yasuo","family":"Ihara","sequence":"additional","affiliation":[{"name":"Ralph Lowell Laboratories, Mailman Research Center, McLean Hospital, and Department of Neurology, Harvard Medical School, Belmont, Massachusetts 02178"}]},{"given":"Fernando J.","family":"Salazar","sequence":"additional","affiliation":[{"name":"Ralph Lowell Laboratories, Mailman Research Center, McLean Hospital, and Department of Neurology, Harvard Medical School, Belmont, Massachusetts 02178"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF00692056","volume":"37","year":"1977","unstructured":"BALL, M.J., NEURONAL LOSS, NEUROFIBRILLARY TANGLES AND GRANULOVACUOLAR DEGENERATION IN HIPPOCAMPUS WITH AGING AND DEMENTIA - 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