Increased cerebral cortical lipid peroxidation and abnormal phospholipids in aged homozygous apoE-deficient C57BL/6J mice.
Aged homozygous apolipoprotein E gene-deficient (apoE -/-) mice have been proposed as an experimental model for the role of human apoE isoforms in Alzheimer's disease (AD). However, results from different laboratories have been in conflict regarding the presence or absence of neurodegeneration in these mice. Moreover, despite apoE being the major lipid trafficking molecule in the central nervous system, there has been no investigation of brain lipid levels in apoE -/- mice. Here we have examined male and female apoE -/- and control mice aged 10 to 12 months, testing the hypothesis that lack of apoE leads to some of the neuropathological changes seen in AD. Our results failed to demonstrate significant neurodegeneration, histopathological changes, or reduction in cerebral cortical synaptophysin in apoE -/- mice. However, we did observe a significant reduction in cerebral cortical phospholipids and their constituent fatty acids, as well as elevated lipid peroxidation products, in apoE -/- mice compared to apoE +/+ mice with the same genetic background. Our results suggest that the brains of aged apoE -/- mice display some of the lipid abnormalities associated with AD; however, these changes alone, at the magnitudes achieved in the apoE -/- mice, do not directly lead to the major neurodegenerative changes of AD.
Montine
T J
TJ
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Montine
K S
KS
Olson
S J
SJ
Graham
D G
DG
Roberts
L J
LJ
Morrow
J D
JD
Linton
M F
MF
Fazio
S
S
Swift
L L
LL
D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006720:Homozygote; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010743:Phospholipids / Q000378:metabolism*
D001057:Apolipoproteins E; D010743:Phospholipids