{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:39:13Z","timestamp":1790937553518,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,4,29]]},"abstract":"<jats:p>\n                    Mounting evidence suggests that defects in energy metabolism contribute to the pathogenesis of Alzheimer disease (AD). Cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    oxidase (CO) is kinetically abnormal, and its activity is decreased in brain and peripheral tissue in late-onset AD. CO is encoded by both the mitochondrial and the nuclear genomes. Its catalytic centers, however, are encoded exclusively by two mitochondrial genes,\n                    <jats:italic>CO1<\/jats:italic>\n                    and\n                    <jats:italic>CO2<\/jats:italic>\n                    (encoding CO subunits I and II, respectively). We searched these genes, as well as other mitochondrial genes, for mutations that might alter CO activity and cosegregate with AD. In the present study, specific missense mutations in the mitochondrial\n                    <jats:italic>CO1<\/jats:italic>\n                    and\n                    <jats:italic>CO2<\/jats:italic>\n                    genes but not the\n                    <jats:italic>CO3<\/jats:italic>\n                    gene were found to segregate at a higher frequency with AD compared with other neurodegenerative or metabolic diseases. These mutations appear together in the same mitochondrial DNA molecule and define a unique mutant mitochondrial genome. Asymptomatic offspring of AD mothers had higher levels of these mutations than offspring of AD fathers, suggesting that these mutations can be maternally inherited. Cell lines expressing these mutant mitochondrial DNA molecules exhibited a specific decrease in CO activity and increased production of reactive oxygen species. We suggest that specific point mutations in the\n                    <jats:italic>CO1<\/jats:italic>\n                    and\n                    <jats:italic>CO2<\/jats:italic>\n                    genes cause the CO defect in AD. A CO defect may represent a primary etiologic event, directly participating in a cascade of events that results in AD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.9.4526","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:43:20Z","timestamp":1027680200000},"page":"4526-4531","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":284,"title":["RETRACTED: Mutations in mitochondrial cytochrome\n                    <i>c<\/i>\n                    oxidase genes segregate with late-onset\u2009Alzheimer\u2009disease"],"prefix":"10.1073","volume":"94","author":[{"given":"Robert E.","family":"Davis","sequence":"first","affiliation":[{"name":"MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92161; Department of Neurology, San Diego Veterans Affairs Medical Center, San Diego, CA 92161; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114; Biology Division, University of Texas Medical Branch, Galveston, TX 77550; and Department of Neurology and Pediatrics,  School of Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Miller","sequence":"additional","affiliation":[{"name":"MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92161; Department of Neurology, San Diego Veterans Affairs Medical Center, San Diego, CA 92161; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114; Biology Division, University of Texas Medical Branch, Galveston, TX 77550; and Department of Neurology and Pediatrics,  School of Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Herrnstadt","sequence":"additional","affiliation":[{"name":"MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92161; Department of Neurology, San Diego Veterans Affairs Medical Center, San Diego, CA 92161; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114; Biology Division, University of Texas Medical Branch, Galveston, TX 77550; and Department of Neurology and Pediatrics,  School of Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumitra S.","family":"Ghosh","sequence":"additional","affiliation":[{"name":"MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92161; Department of Neurology, San Diego Veterans Affairs Medical Center, San Diego, CA 92161; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114; Biology Division, University of Texas Medical Branch, Galveston, TX 77550; and Department of Neurology and Pediatrics,  School of Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eoin","family":"Fahy","sequence":"additional","affiliation":[{"name":"MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92161; Department of Neurology, San Diego Veterans Affairs Medical Center, San Diego, CA 92161; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114; Biology Division, University of Texas Medical Branch, Galveston, TX 77550; and Department of Neurology and Pediatrics,  School of Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie A.","family":"Shinobu","sequence":"additional","affiliation":[{"name":"MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92161; Department of Neurology, San Diego Veterans Affairs Medical Center, San Diego, CA 92161; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114; Biology Division, University of Texas Medical Branch, Galveston, TX 77550; and Department of Neurology and Pediatrics,  School of Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Galasko","sequence":"additional","affiliation":[{"name":"MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92161; Department of Neurology, San Diego Veterans Affairs Medical Center, San Diego, CA 92161; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114; Biology Division, University of Texas Medical Branch, Galveston, TX 77550; and Department of Neurology and Pediatrics,  School of Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon J.","family":"Thal","sequence":"additional","affiliation":[{"name":"MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92161; Department of Neurology, San Diego Veterans Affairs Medical Center, San Diego, CA 92161; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114; Biology Division, University of Texas Medical Branch, Galveston, TX 77550; and Department of Neurology and Pediatrics,  School of Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Flint","family":"Beal","sequence":"additional","affiliation":[{"name":"MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92161; Department of Neurology, San Diego Veterans Affairs Medical Center, San Diego, CA 92161; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114; Biology Division, University of Texas Medical Branch, Galveston, TX 77550; and Department of Neurology and Pediatrics,  School of Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Howell","sequence":"additional","affiliation":[{"name":"MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92161; Department of Neurology, San Diego Veterans Affairs Medical Center, San Diego, CA 92161; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114; Biology Division, University of Texas Medical Branch, Galveston, TX 77550; and Department of Neurology and Pediatrics,  School of Medicine, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"W. 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