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Alliance"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Apolipoprotein E (APOE) effects on brain function remain controversial. Removal of APOE not only impairs cognitive functions but also reduces neuritic amyloid plaques in mouse models of Alzheimer\u2019s disease (AD). Can APOE simultaneously protect and impair neural circuits? Here, we dissociated the role of APOE in AD versus aging to determine its effects on neuronal function and synaptic integrity. Using two-photon calcium imaging in awake mice to record visually evoked responses, we found that genetic removal of APOE improved neuronal responses in adult APP\/PSEN1 mice (8\u201310 mo). These animals also exhibited fewer neuritic plaques with less surrounding synapse loss, fewer neuritic dystrophies, and reactive glia. Surprisingly, the lack of APOE in aged mice (18\u201320 mo), even in the absence of amyloid, disrupted visually evoked responses. These results suggest a dissociation in APOE\u2019s role in AD versus aging: APOE may be neurotoxic during early stages of amyloid deposition, although being neuroprotective in latter stages of aging.<\/jats:p>","DOI":"10.26508\/lsa.201900325","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T22:05:45Z","timestamp":1550095545000},"page":"e201900325","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Opposing Roles of apolipoprotein E in aging and neurodegeneration"],"prefix":"10.26508","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3654-9663","authenticated-orcid":true,"given":"Eloise","family":"Hudry","sequence":"first","affiliation":[{"name":"Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Klickstein","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cannavo","sequence":"additional","affiliation":[{"name":"Centre for Discovery Brain Sciences, UK Dementia Research Institute, and Edinburgh Neuroscience, The University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Jackson","sequence":"additional","affiliation":[{"name":"Centre for Discovery Brain Sciences, UK Dementia Research Institute, and Edinburgh Neuroscience, The University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alona","family":"Muzikansky","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. 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