Murine versus human apolipoprotein E4: differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models

• DOI: 10.1186/s40478-015-0250-y
• Publication Date: 2015-11-10T12:44:56Z
• Authors: Fan Liao; Tony J. Zhang; Hong Jiang; Katheryn B. Lefton; Grace O. Robinson; Robert Vassar; Patrick M. Sullivan; David M. Holtzman
• Keywords: Amyloid (mycology); Apolipoprotein E

Amyloid β (Aβ) accumulates in the extracellular space as diffuse and neuritic plaques Alzheimer's disease (AD). Aβ also deposits on walls of arterioles cerebral amyloid angiopathy (CAA) most cases AD sometimes independently AD. Apolipoprotein E (apoE) ɛ4 is associated with increases both CAA humans. Studies mouse models that develop deposition have shown murine apoE human apoE4 different abilities to facilitate plaque or formation when studied independently. To better understand compare effects apoE4, we bred 5XFAD (line 7031) transgenic mice so they expressed one copy under control normal regulatory elements (5XFAD/apoE(m/4)).The 5XFAD/apoE(m/4) contained levels parenchymal were intermediate between 5XFAD/apoE(m/m) 5XFAD/apoE(4/4) mice. In mice, found co-localized much more than did CAA, suggesting differential co-aggregation versus CAA. More importantly, within brain parenchyma apoE, which its own results pronounced earlier formation, while formation. We further confirmed by showing a strong correlation insoluble PS1APP-21/apoE(m/4) without CAA.These studies suggest opposing influencing via these two lesions set stage for understanding at molecular level.