RT Journal Article
SR Electronic
T1 Opposing Roles of apolipoprotein E in aging and neurodegeneration
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900325
DO 10.26508/lsa.201900325
VO 2
IS 1
A1 Eloise Hudry
A1 Jacob Klickstein
A1 Claudia Cannavo
A1 Rosemary Jackson
A1 Alona Muzikansky
A1 Sheetal Gandhi
A1 David Urick
A1 Taylie Sargent
A1 Lauren Wrobleski
A1 Allyson D Roe
A1 Steven S Hou
A1 Kishore V Kuchibhotla
A1 Rebecca A Betensky
A1 Tara Spires-Jones
A1 Bradley T Hyman
YR 2019
UL https://www.life-science-alliance.org/content/2/1/e201900325.abstract
AB 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.