Affiliations: [a] Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA
| [b] University of Illinois College of Medicine, IL, USA
| [c] University of Miami/Jackson Healthcare System, Miami, FL, USA
| [d] Alzheimer Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| [e] Research and Development Service, James J. Peters VA Medical Center, Bronx, NY, USA
| [f] Department of Neurology, N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN, USA
| [g]
Geriatric Research Education and Clinical Center (GRECC), Minneapolis VA Health Care System, Minneapolis, MN, USA
Correspondence:
[*]
Correspondence to: Leon M. Tai, Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USA. Tel.: +1 312 355 4795; E-mail: [email protected].
Note: [1] Deceased.
Abstract: APOE2 lowers Alzheimer’s disease (AD) risk; unfortunately, the mechanism remains poorly understood and the use of mice models is problematic as APOE2 homozygosity is associated with hyperlipidemia. In this study, we developed mice that are heterozygous for APOE2 and APOE3 or APOE4 and overexpress amyloid-β peptide (Aβ) (EFAD) to evaluate the effect of APOE2 dosage on Aβ pathology. We found that heterozygous mice do not exhibit hyperlipidemia. Hippocampal but not cortical levels of soluble Aβ42 followed the order E2/2FAD > E2/3FAD≤E3/3FAD and E2/2FAD > E2/4FAD < E4/4FAD without an effect on insoluble Aβ42. These findings offer initial insights on the impact of APOE2 on Aβ pathology.
