Progressive Spatial Memory Impairment, Brain Amyloid Deposition and Changes in Serum Amyloid Levels as a Function of Age in APPswe/PS1dE9 Mice

Author(s): Lu Fu, Yao Sun, Yongqing Guo, Bin Yu, Haihong Zhang, Jiaxin Wu, Xianghui Yu, Hui Wu*, Wei Kong*.

Journal Name: Current Alzheimer Research

Volume 15 , Issue 11 , 2018

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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.

Keywords: Alzheimer`s disease, amyloid deposition, APPswe/PS1dE9 transgenic mice, cerebral Aβ42, cognitive decline, serum Aβ42.

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Article Details

VOLUME: 15
ISSUE: 11
Year: 2018
Page: [1053 - 1061]
Pages: 9
DOI: 10.2174/1567205015666180709112327
Price: $58

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