Session Title: Apolipoprotein-E
Presentation Date: Thursday, March 12 – Friday, March 13 ,2009
ROLE OF PERIPHERAL APOE IN THE PATHOGENESIS OF AD IN A TRANSGENIC MOUSE MODEL
L. Katsouri, E. Anastasopoulou, S. Georgopoulos
Biomedical Research Institute, Academy of Athens, Athens, Greece
Background: It has been established that ApoE modulates the risk of developing Alzheimer's disease (AD); nevertheless the specific role of ApoE in the pathogenesis of the disease remains unclear. Although much of the biology of peripheral ApoE in cholesterol metabolism is understood, its role in the pathogenesis of AD has not been evaluated. The significance of ApoE in amyloid deposition has been revealed in studies using Alzheimer transgenic mice that develop amyloid plaques and express the human apoE alleles on an ApoE deficient background. All these studies address the question of the role of CNS-derived apoE in AD but do not examine the role of peripheral ApoE in AD pathology.
Aim/methods: To elucidate the role of peripheral ApoE in the pathogenesis of AD, we generated a huApoE4 transgenic mouse under a liver-specific promoter (TTRI) and crossed it with an Alzheimer transgenic mouse (5XFAD APP/PS1) on the ApoE-/- background.
Results: We have generated a new huApoE4 transgenic mouse model and crossed it with an Alzheimer mouse model. The 5XFAD/TTRI-hu ApoE4/ApoE-/- as well as the 5XFAD ApoE-/- control mice will be analyzed for amyloid plaque formation, Aβ deposition, Aβ40 and 42 levels and behavioral alterations. Peripheral and brain ApoE and cholesterol levels will also be analysed.
Conclusions: We have generated a transgenic mouse system to evaluate the role of peripheral apoE on AD pathology. These data will be presented.