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U.S.A."],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    This study of the monkey cerebral cortex revealed age-related changes that help to answer key questions about Alzheimer\u2019s disease (AD): (\n                    <jats:italic>i<\/jats:italic>\n                    ) why advancing age is the highest risk factor for AD and (\n                    <jats:italic>ii<\/jats:italic>\n                    ) why neurofibrillary tangles (NFTs) in AD selectively target extensively interconnected pyramidal neurons in the highly evolved association cortex, but do not afflict the primary sensory cortex. NFTs arise from phosphorylation of tau protein. In aged prefrontal association cortex, we found increased cAMP-dependent protein kinase (PKA) phosphorylation of tau and corresponding loss of phosphodiesterase 4A, an enzyme that regulates cAMP-PKA signaling in dendritic spines where pyramidal neurons interconnect. In contrast, phosphorylated tau was not observed in aged primary visual cortex. These data provide new strategies for early intervention in AD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1322360111","type":"journal-article","created":{"date-parts":[[2014,3,19]],"date-time":"2014-03-19T00:08:16Z","timestamp":1395187696000},"page":"5036-5041","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":137,"title":["cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex"],"prefix":"10.1073","volume":"111","author":[{"given":"Becky C.","family":"Carlyle","sequence":"first","affiliation":[{"name":"Departments of aPsychiatry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus C.","family":"Nairn","sequence":"additional","affiliation":[{"name":"Departments of aPsychiatry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Neurobiology, Yale University School of Medicine, New Haven, CT 06511; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Neurobiology, Yale University School of Medicine, New Haven, CT 06511; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu E.","family":"Jin","sequence":"additional","affiliation":[{"name":"Neurobiology, Yale University School of Medicine, New Haven, CT 06511; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur A.","family":"Simen","sequence":"additional","affiliation":[{"name":"Departments of aPsychiatry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Departments of aPsychiatry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Bordner","sequence":"additional","affiliation":[{"name":"Departments of aPsychiatry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E.","family":"Craft","sequence":"additional","affiliation":[{"name":"Departments of aPsychiatry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Davies","sequence":"additional","affiliation":[{"name":"Litwin\u2013Zucker Research Center for the Study of Alzheimer's Disease, Feinstein Institute for Medical Research, North Shore\u2013Long Island Jewish Health System, Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihovil","family":"Pletikos","sequence":"additional","affiliation":[{"name":"Neurobiology, Yale University School of Medicine, New Haven, CT 06511; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nenad","family":"\u0160estan","sequence":"additional","affiliation":[{"name":"Neurobiology, Yale University School of Medicine, New Haven, CT 06511; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy F. 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