TY - JOUR
T1 - Opposing Roles of apolipoprotein E in aging and neurodegeneration
AU - Hudry, Eloise
AU - Klickstein, Jacob
AU - Cannavo, Claudia
AU - Jackson, Rosemary
AU - Muzikansky, Alona
AU - Gandhi, Sheetal
AU - Urick, David
AU - argent, Taylie
AU - Wrobleski, Lauren
AU - Roe, Allyson D.
AU - Hou, Steven S.
AU - Kuchibhotla, Kishore V.
AU - Betensky, Rebecca A.
AU - Spires-Jones, Tara
AU - Hyman, Bradley T.
N1 - Publisher Copyright:
© 2019 Hudry et al.
PY - 2019/2
Y1 - 2019/2
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.
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.
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U2 - 10.26508/LSA.201900325
DO - 10.26508/LSA.201900325
M3 - Article
C2 - 30760557
AN - SCOPUS:85070475389
SN - 2575-1077
VL - 2
JO - Life science alliance
JF - Life science alliance
IS - 1
M1 - e201900325
ER -