TY - JOUR
T1 - Increased cerebral cortical lipid peroxidation and abnormal phospholipids in aged homozygous apoE-deficient C57BL/6J mice
AU - Montine, Thomas J.
AU - Montine, Kathleen S.
AU - Olson, Sandra J.
AU - Graham, Doyle G.
AU - Roberts, L. Jackson
AU - Morrow, Jason D.
AU - Linton, MacRae F.
AU - Fazio, Sergio
AU - Swift, Larry L.
N1 - Funding Information:
We thank Ms. Linda Gleaves, Ms. Kathy Carter, and Ms. Rebecca Meitus for their expert assistance. This work was supported by NIH Grants AG00774, DK48831, GM42056, GM15431, and CA77839 and grants from the Alzheimer’s Disease and Related Disorders Association and the American Foundation for Aging Research.
PY - 1999/7
Y1 - 1999/7
N2 - 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.
AB - 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.
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U2 - 10.1006/exnr.1999.7067
DO - 10.1006/exnr.1999.7067
M3 - Article
C2 - 10448437
AN - SCOPUS:0032839939
SN - 0014-4886
VL - 158
SP - 234
EP - 241
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -