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Review
. 2022 Jun 21:15:912995.
doi: 10.3389/fnmol.2022.912995. eCollection 2022.

Mouse Models of Alzheimer's Disease

Miyabishara Yokoyama  1 , Honoka Kobayashi  1 , Lisa Tatsumi  1 , Taisuke Tomita  1
Affiliations
Review

Mouse Models of Alzheimer's Disease

Miyabishara Yokoyama et al. Front Mol Neurosci. .

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and personality changes, eventually leading to dementia. The pathological hallmarks of AD are senile plaques and neurofibrillary tangles, which comprise abnormally aggregated β-amyloid peptide (Aβ) and hyperphosphorylated tau protein. To develop preventive, diagnostic, and therapeutic strategies for AD, it is essential to establish animal models that recapitulate the pathophysiological process of AD. In this review, we will summarize the advantages and limitations of various mouse models of AD, including transgenic, knock-in, and injection models based on Aβ and tau. We will also discuss other mouse models based on neuroinflammation because recent genetic studies have suggested that microglia are crucial in the pathogenesis of AD. Although each mouse model has its advantages and disadvantages, further research on AD pathobiology will lead to the establishment of more accurate mouse models, and accelerate the development of innovative therapeutics.

Keywords: Alzheimer’s disease; mouse model; tau; therapeutics; β-amyloid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Aβ production from APP. (A) Schematic depiction of the Aβ production pathway. APP is sequentially cleaved by β- and γ-secretases to release Aβ into the extracellular space. Aβ monomer is prone to aggregate, forming oligomers, protofibrils, and fibrils. (B) Diagram of the APP (above) and sequence of Aβ (below). The transmembrane segment (TM) is highlighted in yellow. The bold letters below the Aβ sequence indicate the missense FAD mutations within the Aβ sequence. The above and below the number of the Aβ sequence follow the numbering of the longest isoform of APP and Aβ amino acid sequence, respectively.
Figure 2
Figure 2
Tau isoforms in the human brain. (A) Schematic depiction of the formation of neurofibrillary tangles. Tau protein control stabilization of microtubules by kinases. Phosphorylated tau leads to microtubule disassembly. Irregular hyperphosphorylation of tau proteins results in the generation of insoluble tau oligomers, which then accumulate to form PHF, then NFT. (B) Schematic diagram of tau isoforms that are expressed in the adult human brain. MAPT gene encodes tau protein. The six tau isoforms are generated by splicing of exons 2, 3, and/or 10 that encode for N1 (blue), N2 (yellow), and R2 (red), respectively. The inclusion of exon 10 results in the generation of mRNA encoding 4R tau. The location of missense MAPT mutations utilized in the transgenic mice is shown.
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