TY - JOUR
T1 - Cognitive deficits in human ApoE4 knock-in mice
T2 - A systematic review and meta-analysis
AU - van Heuvelen, Marieke J.G.
AU - van der Lei, Mathijs B.
AU - Alferink, Pien M.
AU - Roemers, Peter
AU - van der Zee, Eddy A.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/8/5
Y1 - 2024/8/5
N2 - Apolipoprotein-E4 (ApoE4) is an important genetic risk factor for Alzheimer's disease. The development of targeted-replacement human ApoE knock-in mice facilitates research into mechanisms by which ApoE4 affects the brain. We performed meta-analyses and meta-regression analyses to examine differences in cognitive performance between ApoE4 and ApoE3 mice. We included 61 studies in which at least one of the following tests was assessed: Morris Water Maze (MWM), novel object location (NL), novel object recognition (NO) and Fear Conditioning (FC) test. ApoE4 vs. ApoE3 mice performed significantly worse on the MWM (several outcomes, 0.17 ≤ g ≤ 0.60), NO (exploration, g=0.33; index, g=0.44) and FC (contextual, g=0.49). ApoE4 vs. ApoE3 differences were not systematically related to sex or age. We conclude that ApoE4 knock-in mice in a non-AD condition show some, but limited cognitive deficits, regardless of sex and age. These effects suggest an intrinsic vulnerability in ApoE4 mice that may become more pronounced under additional brain load, as seen in neurodegenerative diseases.
AB - Apolipoprotein-E4 (ApoE4) is an important genetic risk factor for Alzheimer's disease. The development of targeted-replacement human ApoE knock-in mice facilitates research into mechanisms by which ApoE4 affects the brain. We performed meta-analyses and meta-regression analyses to examine differences in cognitive performance between ApoE4 and ApoE3 mice. We included 61 studies in which at least one of the following tests was assessed: Morris Water Maze (MWM), novel object location (NL), novel object recognition (NO) and Fear Conditioning (FC) test. ApoE4 vs. ApoE3 mice performed significantly worse on the MWM (several outcomes, 0.17 ≤ g ≤ 0.60), NO (exploration, g=0.33; index, g=0.44) and FC (contextual, g=0.49). ApoE4 vs. ApoE3 differences were not systematically related to sex or age. We conclude that ApoE4 knock-in mice in a non-AD condition show some, but limited cognitive deficits, regardless of sex and age. These effects suggest an intrinsic vulnerability in ApoE4 mice that may become more pronounced under additional brain load, as seen in neurodegenerative diseases.
KW - Apolipoprotein
KW - Cognition
KW - Fear conditioning
KW - Genotype
KW - Learning
KW - Morris water maze
KW - Novel location
KW - Novel object
KW - Rodent
UR - http://www.scopus.com/inward/record.url?scp=85197746826&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2024.115123
DO - 10.1016/j.bbr.2024.115123
M3 - Review article
C2 - 38972485
AN - SCOPUS:85197746826
SN - 0166-4328
VL - 471
JO - Behavioural Brain Research
JF - Behavioural Brain Research
M1 - 115123
ER -