Laboratory Animal and Comparative Medicine, Volume. 45, Issue 3, 269(2025)
Establishment of a Rat Model of Alzheimer's Disease by Introducing Human Triple Mutant APP Gene into Hippocampus via Brain Stereotactic Technology
[2] [2] SCHELTENS P, DE STROOPER B, KIVIPELTO M, et al. Alzheimer's disease[J]. Lancet, 2021, 397(10284): 1577-1590. DOI: 10.1016/s0140-6736(20)32205-4.
[3] [3] SCHELTENS P, BLENNOW K, BRETELER M M, et al. Alzheimer's disease[J]. Lancet, 2016, 388(10043): 505-517. DOI: 10.1016/s0140-6736(15)01124-1.
[4] [4] BREIJYEH Z, KARAMAN R. Comprehensive review on Alzheimer's disease: causes and treatment[J]. Molecules, 2020, 25(24): 5789. DOI: 10.3390/molecules25245789.
[5] [5] JUCKER M, WALKER L C. Alzheimer's disease: From immunotherapy to immunoprevention[J]. Cell, 2023, 186(20): 4260-4270. DOI: 10.1016/j.cell.2023.08.021.
[6] [6] ZHOU B, LU J G, SIDDU A, et al. Synaptogenic effect ofAPP-Swedish mutation in familial Alzheimer's disease[J]. Sci Transl Med, 2022, 14(667): eabn9380. DOI: 10.1126/scitranslmed.abn9380.
[7] [7] KIM M, BEZPROZVANNY I. Analysis of non-amyloidogenic mutations in APP supports loss of function hypothesis of Alzheimer's disease[J]. Int J Mol Sci, 2023, 24(3): 2092. DOI: 10.3390/ijms24032092.
[8] [8] ARMBRUST F, BICKENBACH K, MARENGO L, et al. The Swedish dilemma - the almost exclusive use of APPswe-based mouse models impedes adequate evaluation of alternative -secretases[J]. Biochim Biophys Acta Mol Cell Res, 2022, 1869(3): 119164. DOI: 10.1016/j.bbamcr.2021.119164.
[9] [9] SCHILLING S, PRADHAN A, HEESCH A, et al. Differential effects of familial Alzheimer's disease-causing mutations on amyloid precursor protein (APP) trafficking, proteolytic conversion, and synaptogenic activity[J]. Acta Neuropathol Commun, 2023, 11(1): 87. DOI: 10.1186/s40478-023-01577-y.
[10] [10] JAWORSKI T, DEWACHTER I, LECHAT B, et al. AAV-tau mediates pyramidal neurodegeneration by cell-cycle re-entry without neurofibrillary tangle formation in wild-type mice[J]. PLoS One, 2009, 4(10): e7280. DOI: 10.1371/journal.pone.0007280.
[11] [11] XIA D, LIANOGLOU S, SANDMANN T, et al. Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia[J]. Mol Neurodegener, 2022, 17(1): 41. DOI: 10.1186/s13024-022-00547-7.
[12] [12] CLAYTON K, DELPECH J C, HERRON S, et al. Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model[J]. Mol Neurodegener, 2021, 16(1): 18. DOI: 10.1186/s13024-021-00440-9.
[13] [13] TESSON L, COZZI J, MNORET S, et al. Transgenic modifications of the rat genome[J]. Transgenic Res, 2005, 14 (5): 531-546. DOI: 10.1007/s11248-005-5077-z.
[14] [14] PANG K L, JIANG R C, ZHANG W, et al. An App knock-in rat model for Alzheimer's disease exhibiting A and tau pathologies, neuronal death and cognitive impairments[J]. Cell Res, 2022, 32(2): 157-175. DOI: 10.1038/s41422-021-00582-x.
[15] [15] PUPO A, FERNNDEZ A, LOW S H, et al. AAV vectors: The Rubik's cube of human gene therapy[J]. Mol Ther, 2022, 30(12): 3515-3541. DOI: 10.1016/j.ymthe.2022.09.015.
[16] [16] ASCHAUER D F, KREUZ S, RUMPEL S. Analysis of transduction efficiency, tropism and axonal transport of AAV serotypes 1, 2, 5, 6, 8 and 9 in the mouse brain[J]. PLoS One, 2013, 8(9): e76310. DOI: 10.1371/journal.pone.0076310.
[17] [17] ROSTAGNO A A. Pathogenesis of Alzheimer's disease[J]. Int J Mol Sci, 2022, 24(1): 107. DOI: 10.3390/ijms24010107.
[18] [18] KAYED R, LASAGNA-REEVES C A. Molecular mechanisms of amyloid oligomers toxicity[J]. J Alzheimers Dis, 2013, 33(Suppl 1): S67-S78. DOI: 10.3233/JAD-2012-129001.
[19] [19] FOLKESSON R, MALKIEWICZ K, KLOSKOWSKA E, et al. A transgenic rat expressing human APP with the Swedish Alzheimer's disease mutation[J]. Biochem Biophys Res Commun, 2007, 358(3): 777-782. DOI: 10.1016/j.bbrc.2007.04.195.
[20] [20] KLOSKOWSKA E, PHAM T M, NILSSON T, et al. Cognitive impairment in the Tg6590 transgenic rat model of Alzheimer's disease[J]. J Cell Mol Med, 2010, 14(6B): 1816-1823. DOI: 10.1111/j.1582-4934.2009.00809.x.
[21] [21] FENG W X, ZHANG Y L, WANG Z, et al. Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer's disease mouse model with suppression of glymphatic clearance[J]. Alzheimers Res Ther, 2020, 12(1): 125. DOI: 10.1186/s13195-020-00688-1.
[22] [22] LI Z Y, ZHANG Y, MENG X B, et al. A novel DPP-4 inhibitor Gramcyclin A attenuates cognitive deficits in APP/PS1/tau triple transgenic miceviaenhancing brain GLP-1-dependent glucose uptake[J]. Phytother Res, 2022, 36(3): 1297-1309. DOI: 10.1002/ptr.7387.
[23] [23] HAMPTON D W, WEBBER D J, BILICAN B, et al. Cell-mediated neuroprotection in a mouse model of human tauopathy[J]. J Neurosci, 2010, 30(30): 9973-9983. DOI: 10.1523/JNEUROSCI.0834-10.2010.
[24] [24] KIM H Y, LEE D K, CHUNG B R, et al. Intracerebroventricular injection of amyloid- peptides in normal mice to acutely induce Alzheimer-like cognitive deficits[J]. J Vis Exp, 2016 (109): 53308. DOI: 10.3791/53308.
[25] [25] SU Y C, WALKER J R, PARK Y, et al. Novel NanoLuc substrates enable bright two-population bioluminescence imaging in animals[J]. Nat Methods, 2020, 17(8): 852-860. DOI: 10.1038/s41592-020-0889-6.
[26] [26] TIAN X D, ZHANG Y Y, LI X Y, et al. A luciferase prosubstrate and a red bioluminescent calcium indicator for imaging neuronal activity in mice[J]. Nat Commun, 2022, 13(1): 3967. DOI: 10.1038/s41467-022-31673-x.
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XIAO Linlin, YANG Yixuan, LI Shanshan, LUO Lanshiyu, YIN Siwei, SUN Juming, SHI Wei, OUYANG Yiqiang, LI Xiyi. Establishment of a Rat Model of Alzheimer's Disease by Introducing Human Triple Mutant APP Gene into Hippocampus via Brain Stereotactic Technology[J]. Laboratory Animal and Comparative Medicine, 2025, 45(3): 269
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Received: Mar. 1, 2025
Accepted: Aug. 26, 2025
Published Online: Aug. 26, 2025
The Author Email: LI Xiyi (leeciyee@163.com)
