Human apolipoprotein E4 accelerates β‐amyloid deposition in APPsw transgenic mouse brain
- 6 August 2001
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 50 (4) , 468-475
- https://doi.org/10.1002/ana.1134
Abstract
The human apolipoprotein E4 (ApoE4) isoform is associated with genetic risk for Alzheimer's disease. To assess the effects of different ApoE isoforms on amyloid plaque formation, human ApoE3 and ApoE4 were expressed in the brains of transgenic mice under the control of the human transferrin promoter. Mice were crossed with transgenic mice expressing human amyloid precursor protein containing the Swedish mutation (APPsw), which facilitates amyloid β peptide (Aβ) production. The following progeny were selected for characterization: APPsw+/– × ApoE3+/– and APPsw+/–, APPsw+/– × ApoE4+/– and APPsw+/– littermates. All mice analyzed were wild type for the endogenous mouse APP and ApoE genes. Mice expressing ApoE4 in combination with APPsw have accelerated Aβ deposition in the brain as assessed by enzyme immunoassay for Aβ40 and Aβ42 extractable in 70% formic acid, by assessment of amyloid plaque formation using thioflavin-S staining, and by immunohistochemical staining with antibodies specific for Aβ40 or Aβ42 and the 4G8 monoclonal or 162 polyclonal antibody. No difference in the rate of Aβ deposition in the brain was seen in mice expressing ApoE3 in combination with APPsw. Thus, our data are consistent with the observation in Alzheimer's disease that ApoE4 is associated with increased accumulation of Aβ in the brain relative to ApoE3.Keywords
This publication has 28 references indexed in Scilit:
- Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease modelAnnals of Neurology, 2000
- Detection of Apolipoprotein E/Dimeric Soluble Amyloid β Complexes in Alzheimer's Disease Brain SupernatantsBiochemical and Biophysical Research Communications, 1997
- Lack of apolipoprotein E dramatically reduces amyloid β-peptide depositionNature Genetics, 1997
- Characterization of the Binding of Amyloid‐β Peptide to Cell Culture‐Derived Native Apolipoprotein E2, E3, and E4 Isoforms and to Isoforms from Human PlasmaJournal of Neurochemistry, 1997
- Human APOE protein localized in brains of transgenic miceNeuroscience Letters, 1996
- Characterization of stable complexes involving apolipoprotein E and the amyloid β peptide in Alzheimer's disease brainNeuron, 1995
- Elevated Aβ levels in Alzheimer's disease brain are associated with selective accumulation of Aβ42 in parenchymal amyloid plaques and both Aβ40 and Aβ42 in cerebrovascular depositsAmyloid, 1995
- Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43)Neuron, 1994
- Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.Proceedings of the National Academy of Sciences, 1993
- Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactionsNeuron, 1993