Human apolipoprotein E4 accelerates β‐amyloid deposition in APPsw transgenic mouse brain

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 Aβ 40 and Aβ 42 extractable in 70% formic acid, by assessment of amyloid plaque formation using thioflavin‐S staining, and by immunohistochemical staining with antibodies specific for Aβ 40 or Aβ 42 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.