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Using 5\u00d7<jats:styled-content style=\"fixed-case\">FAD<\/jats:styled-content> transgenic mice, which develop robust <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> pathology and memory deficits when very young, we detected interactions between clusterin and A\u00df in the mouse brains. The two proteins were concurrently upregulated and bound or colocalized with each other in the same complexes or in amyloid plaques. Neuropathology and cognitive performance were assessed in the progeny of clusterin\u2010null mice crossed with 5\u00d7<jats:styled-content style=\"fixed-case\">FAD<\/jats:styled-content> mice, yielding <jats:italic>clu<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>;5\u00d7<jats:styled-content style=\"fixed-case\">FAD<\/jats:styled-content> and <jats:italic>clu<\/jats:italic><jats:sup>+\/+<\/jats:sup>;5\u00d7<jats:styled-content style=\"fixed-case\">FAD<\/jats:styled-content>. We found far less of the various pools of A\u00df proteins, most strikingly soluble A\u00df oligomers and amyloid plaques in <jats:italic>clu<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>;5\u00d7<jats:styled-content style=\"fixed-case\">FAD<\/jats:styled-content> mice at 5 months of age. At that age, those mice also had higher levels of neuronal and synaptic proteins and better motor coordination, spatial learning and memory than age\u2010matched <jats:italic>clu<\/jats:italic><jats:sup>+\/+<\/jats:sup>;5\u00d7<jats:styled-content style=\"fixed-case\">FAD<\/jats:styled-content> mice. However, at 10 months of age, these differences disappeared, with A\u00df and plaque deposition, neuronal and synaptic proteins and impairment of behavioral and cognitive performance similar in both groups. These findings demonstrate that clusterin is necessarily involved in early stages of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> pathogenesis by enhancing toxic A\u00df pools to cause A\u00df\u2010directed neurodegeneration and behavioral and cognitive impairments, but not in late stage.<\/jats:p>","DOI":"10.1111\/bpa.12660","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T09:15:01Z","timestamp":1538990101000},"page":"217-231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Clusterin contributes to early stage of Alzheimer's disease pathogenesis"],"prefix":"10.1111","volume":"29","author":[{"given":"Shin\u2010Bi","family":"Oh","sequence":"first","affiliation":[{"name":"Asan Institute for Life Sciences Asan Medical Center Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min 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