Title:Progressive Spatial Memory Impairment, Brain Amyloid Deposition and Changes in Serum Amyloid Levels as a Function of Age in APPswe/PS1dE9 Mice
VOLUME: 15 ISSUE: 11
Author(s):Lu Fu, Yao Sun, Yongqing Guo, Bin Yu, Haihong Zhang, Jiaxin Wu, Xianghui Yu, Hui Wu* and Wei Kong*
Affiliation:National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012
Keywords:Alzheimer`s disease, amyloid deposition, APPswe/PS1dE9 transgenic mice, cerebral Aβ42, cognitive decline, serum
Aβ42.
Abstract:Background: Mice co-expressing human amyloid precursor protein with the Swedish mutation
(APPswe) and exon-9-deleted presenilin (PS1dE9) has become one of the most widely used mouse
models for studying Alzheimer’s disease (AD) pathogenesis and preclinical studies of AD therapeutic
approaches.
Objective: In this study, we systematically investigated cognitive decline, amyloid-β (Aβ) deposition
and cerebral or Aβ serum levels as well as the relationships among these measures in APPswe/PS1dE9
transgenic mice.
Method: APPswe/PS1dE9 mice were separated into four equal age cohorts (4, 6, 9, and 12 months). We
assessed cognitive capacity, deposited plaques, and the levels of Aβ40/Aβ42 in brain tissue and serum of
mice at different ages.
Results: APPswe/PS1dE9 mice exhibited declined memory beginning at 6 months of age, with cognitive
capacity remarkably impaired at 12-months. Coincidently, amyloid deposits began to develop in transgenic
mice brain at 6-months and increased with age. In addition, Aβ42 levels in brains of APPswe/
PS1dE9 mice increased with age with no parallel increase in Aβ40. The concentration of serum
Aβ42 declined from 4 to 6 months of age, but a similar age-dependent decrease was not observed for
Aβ40.
Conclusion: APPswe/PS1dE9 transgenic mice began to develop amyloid plaques at 6 months of age and
exhibited a corresponding impairment of spatial learning capacity. Serum Aβ42 level decreased remarkably
from 4 to 6 months, at which stage Aβ42 began to accumulate in the brain and deposit as
plaques.
