TY - JOUR T1 - Opposing Roles of apolipoprotein E in aging and neurodegeneration JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900325 VL - 2 IS - 1 SP - e201900325 AU - Eloise Hudry AU - Jacob Klickstein AU - Claudia Cannavo AU - Rosemary Jackson AU - Alona Muzikansky AU - Sheetal Gandhi AU - David Urick AU - Taylie Sargent AU - Lauren Wrobleski AU - Allyson D Roe AU - Steven S Hou AU - Kishore V Kuchibhotla AU - Rebecca A Betensky AU - Tara Spires-Jones AU - Bradley T Hyman Y1 - 2019/02/01 UR - https://www.life-science-alliance.org/content/2/1/e201900325.abstract N2 - 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’s 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 (8–10 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 (18–20 mo), even in the absence of amyloid, disrupted visually evoked responses. These results suggest a dissociation in APOE’s role in AD versus aging: APOE may be neurotoxic during early stages of amyloid deposition, although being neuroprotective in latter stages of aging. ER -