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APP mouse models for Alzheimer's disease preclinical studies
Hiroki Sasaguri1,2, Per Nilsson3,4, Shoko Hashimoto3
1Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Japan hiroki.sasaguri@riken.jp saido@brain.riken.jp.
The EMBO Journal
|August 4, 2017
Summary
This review examines Alzheimer's disease (AD) mouse models. Second-generation models offer improved recapitulation of AD pathology without overexpression issues seen in older transgenic models.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Accurate animal models are crucial for Alzheimer's disease (AD) research and preclinical studies.
- First-generation transgenic (Tg) mouse models overexpress familial AD (FAD) proteins, potentially causing non-AD phenotypes.
- Second-generation mouse models feature humanized sequences and mutations in the endogenous mouse App gene, reducing overexpression artifacts.
Purpose of the Study:
- To evaluate various amyloid precursor protein (APP) mouse models for Alzheimer's disease (AD).
- To review recent studies utilizing second-generation APP mouse models.
- To guide AD researchers in selecting appropriate models based on study goals.
Main Methods:
- Literature review of existing Alzheimer's disease (AD) mouse models.
- Analysis of studies employing second-generation APP mouse models.
- Comparative assessment of model strengths and limitations.
Main Results:
- First-generation Tg models exhibit AD pathology but may have confounding phenotypes due to protein overexpression.
- Second-generation models show amyloid-beta (Aβ) accumulation without overexpression issues, but are not yet a complete clinical recapitulation of human AD.
- Recent studies highlight the utility of second-generation models in AD research.
Conclusions:
- Second-generation APP mouse models represent an advancement over first-generation models for studying AD.
- Researchers should carefully consider the specific strengths and limitations of each model for their preclinical studies.
- Choosing the right model is critical for advancing understanding and therapeutic development in Alzheimer's disease.
