title: EFAD transgenic mice as a humanAPOErelevant preclinical model of Alzheimer's disease.
abstract: Identified in 1993,APOE4is the greatest genetic risk factor for sporadic Alzheimer's disease (AD), increasing risk up to 15-fold compared withAPOE3, withAPOE2decreasing AD risk. However, the functional effects ofAPOE4on AD pathology remain unclear and, in some cases, controversial. In vivo progress to understand how the human (h)-APOEgenotypes affect AD pathology has been limited by the lack of a tractable familial AD-transgenic (FAD-Tg) mouse model expressing h-APOErather than mouse (m)-APOE.The disparity between m- and h-apoE is relevant for virtually every AD-relevant pathway, including amyloid-β (Aβ) deposition and clearance, neuroinflammation, tau pathology, neural plasticity and cerebrovascular deficits. EFAD mice were designed as a temporally useful preclinical FAD-Tg-mouse model expressing the h-APOEgenotypes for identifying mechanisms underlyingAPOE-modulated symptoms of AD pathology. From their first description in 2012, EFAD mice have enabled critical basic and therapeutic research. Here we review insights gleaned from the EFAD mice and summarize future directions.
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612.
authors.forename: Leon M
authors.initials: LM
authors.lastname: Tai
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612.
authors.forename: Deebika
authors.initials: D
authors.lastname: Balu
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612.
authors.forename: Evangelina
authors.initials: E
authors.lastname: Avila-Munoz
authors.affiliation: Roskamp Institute, Sarasota, FL 34234.
authors.forename: Laila
authors.initials: L
authors.lastname: Abdullah
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612.
authors.forename: Riya
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612.
authors.forename: Nicole
authors.initials: N
authors.lastname: Collins
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Valencia-Olvera
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612. Electronic address: mladu@uic.edu.
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: LaDu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D053327:Apolipoprotein E4 / Q000097:blood / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype
chemical_list: D053327:Apolipoprotein E4
keywords: EFAD; animal models; apolipoprotein E; apolipoprotein E lipidation; apolipoproteins; behavior; brain; cerebrovascular dysfunction; histopathology; lipoproteins; neuronal viability