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P4‐050: Dysregulation of brain ApoE and cholesterol metabolism in APP transgenic mice
Author(s) -
Warwick Helen K.,
Jefferson Julius,
Atchison Kevin,
Zhou Hua,
Kirksey Yolanda,
Gonzales Cathleen,
Aschmies Suzan,
Jacobsen J.S.,
Pangalos Menelas N.,
Reinhart Peter H.,
Riddell David R.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.920
Subject(s) - lrp1 , apolipoprotein e , genetically modified mouse , transgene , ldl receptor , biology , endocrinology , activator (genetics) , medicine , plasminogen activator , receptor , amyloid precursor protein , cholesterol , lipoprotein , gene , biochemistry , alzheimer's disease , disease
months (p<0.002), respectively. Likewise, IHC analysis revealed an 83% increase in PHF1 IR tau in the pyriform cortex at 8-9 months, (p1⁄40.02), and a comparable increase at 5-6 months and in AT8 IR (IHC and Western) that are being quantitated. Importantly, the htau/PS1/mtau-/mice were more cognitively impaired than controls in the Radial Arm Maze (p<0.03). Analyses of other cortical and hippocampal regions with advanced tau pathology, with other tau antibodies as well as of insoluble tau is underway. Furthermore, older animals, tau-related pathology and the potential involvement of various signaling pathways are being assessed. Conclusions: The M146L mutation promotes age-related tau phosphorylation and aggregation, and impairs cognition compared to controls, suggesting that PS1/tau interaction may be important in the etiology and/or pathogenesis of AD. This novel model can be very useful for studying the onset and progression of AD as well as for therapeutic studies.