Characteristics and Application of Transgenic Mouse Models in Alzheimer's Disease

doi:10.12300/j.issn.1674-5817.2021.182

Abstract

Abstract:

Alzheimer's disease is a common neurodegenerative disease characterized by progressive memory loss and overall cognitive decline. Two typical pathological features are senile plaques and neurofibrillary tangles detected in the brain, which consist of large amounts of precipitated amyloid peptide and hyperphosphorylated Tau protein, respectively. In addition, there are other pathological features such as neuroinflammatory response and extensive loss of neurons. In the past decades, a lot of research has been done on Alzheimer's disease, but its etiology and pathogenesis are still unclear, and there is no ideal treatment or radical cure. This review introduced the characteristics of various transgenic animal models and their current application in preclinical studies, in order to provide theoretical basis for future experimental studies.

Key words: Alzheimer's disease, Transgenic mouse, Animal models, β-amyloid protein, Tau protein

CLC Number:

Q95-33

Feng WEI, Weiwei CHENG, Yafu YIN. Characteristics and Application of Transgenic Mouse Models in Alzheimer's Disease[J]. Laboratory Animal and Comparative Medicine, 2022, 42(5): 432-439.

References 45

1	JIA L F, DU Y F, CHU L, et al. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study[J]. Lancet Public Health, 2020, 5(12): e661-e671. DOI:10.1016/S2468-2667(20)30185-7 .
2	WANG Y Q, JIA R X, LIANG J H, et al. Dementia in China (2015-2050) estimated using the 1% population sampling survey in 2015[J]. Geriatr Gerontol Int, 2019, 19(11):1096-1100. DOI:10.1111/ggi.13778 .
3	中国老龄协会.认知症老年人照护服务现状与发展报告[EB/OL].(2021-05-12)[2021-05-13]. .
4	BALLARD C, GAUTHIER S, CORBETT A, et al. Alzheimer's disease[J]. Lancet, 2011, 377(9770):1019-1031. DOI:10.1016/S0140-6736(10)61349-9 .
5	WELLER J, BUDSON A. Current understanding of Alzheimer's disease diagnosis and treatment[J]. F1000Res, 2018, 7: F1000 Faculty Rev-F1000 Faculty1161. DOI:10.12688/f1000research.14506.1 .
6	HANE F T, LEE B Y, LEONENKO Z. Recent progress in Alzheimer's disease research, part 1: pathology[J]. J Alzheimers Dis, 2017, 57(1):1-28. DOI:10.3233/JAD-160882 .
7	JONSSON T, ATWAL J K, STEINBERG S, et al. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline[J]. Nature, 2012, 488(7409):96-99. DOI:10.1038/nature11283 .
8	CHONG F P, NG K Y, KOH R Y, et al. Tau proteins and tauopathies in Alzheimer's disease[J].Cell Mol Neurobiol, 2018, 38(5):965-980. DOI:10.1007/s10571-017-0574-1 .
9	SAITO T, MATSUBA Y, MIHIRA N, et al. Single App knock-in mouse models of Alzheimer's disease[J]. Nat Neurosci, 2014, 17(5):661-663. DOI:10.1038/nn.3697 .
10	Masliah E, Sisk A, Mallory M, et al. Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer's disease [J]. J Neurosci, 1996, 16(18): 5795-5811.
11	CHEN G Q, CHEN K S, KNOX J, et al. A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease[J]. Nature, 2000, 408(6815):975-979. DOI:10.1038/35050103 .
12	BEGLOPOULOS V, TULLOCH J, ROE A D, et al. Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice[J]. Nat Commun, 2016, 7:11761. DOI:10.1038/ncomms11761 .
13	SCOPA C, MARROCCO F, LATINA V, et al. Impaired adult neurogenesis is an early event in Alzheimer's disease neurodegeneration, mediated by intracellular Aβ oligomers[J]. Cell Death Differ, 2020, 27(3):934-948. DOI:10.1038/s41418-019-0409-3 .
14	KAWARABAYASHI T, YOUNKIN L H, SAIDO T C, et al. Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease[J]. J Neurosci, 2001, 21(2):372-381. DOI:10.1523/JNEUROSCI.21-02-00372.2001 .
15	DAM D V, VLOEBERGHS E, ABRAMOWSKI D, et al. APP23 mice as a model of Alzheimer's disease: an example of a transgenic approach to modeling a CNS disorder[J]. CNS Spectr, 2005, 10(3):207-222. DOI:10.1017/s1092852900010051 .
16	RIJAL UPADHAYA A, SCHEIBE F, KOSTERIN I, et al. The type of Aβ-related neuronal degeneration differs between amyloid precursor protein (APP23) and amyloid β-peptide (APP48) transgenic mice[J]. Acta Neuropathol Commun, 2013, 1(1):77. DOI:10.1186/2051-5960-1-77 .
17	STURCHLER-PIERRAT C, ABRAMOWSKI D, DUKE M, et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology[J]. Proc Natl Acad Sci USA, 1997, 94(24):13287-13292. DOI:10.1073/pnas.94.24.13287 .
18	FLOOD D G, REAUME A G, DORFMAN K S, et al. FAD mutant PS-1 gene-targeted mice: increased Aβ42 and Aβ deposition without APP overproduction[J]. Neurobiol Aging, 2002, 23(3):335-348. DOI:10.1016/S0197-4580(01)00330-X .
19	ZHAO R H, HU W L, TSAI J, et al. Microglia limit the expansion of β-amyloid plaques in a mouse model of Alzheimer's disease[J]. Mol Neurodegeneration, 2017, 12(1):47. DOI:10.1186/s13024-017-0188-6 .
20	SHI Q Q, CHOWDHURY S, MA R, et al. Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice[J]. Sci Transl Med, 2017, 9(392): eaaf6295. DOI:10.1126/scitranslmed.aaf6295 .
21	KIM T K, LEE J E, PARK S K, et al. Analysis of differential plaque depositions in the brains of Tg2576 and Tg-APPswe/PS1dE9 transgenic mouse models of Alzheimer disease[J]. Exp Mol Med, 2012, 44(8):492-502. DOI:10.3858/emm.2012.44.8.056 .
22	EIMER W A, VASSAR R. Neuron loss in the 5XFAD mouse model of Alzheimer's disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation[J]. Mol Neurodegener, 2013, 8:2. DOI:10.1186/1750-1326-8-2 .
23	MAZI A R, ARZUMAN A S, GUREL B, et al. Neonatal neurodegeneration in Alzheimer's disease transgenic mouse model[J]. J Alzheimers Dis Rep, 2018, 2(1):79-91. DOI:10.3233/ADR-170049 .
24	HSIAO K, CHAPMAN P, NILSEN S, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice[J]. Science, 1996, 274(5284):99-102. DOI:10.1126/science.274.5284.99 .
25	SPANGENBERG E E, LEE R J, NAJAFI A R, et al. Eliminating microglia in Alzheimer's mice prevents neuronal loss without modulating amyloid-β pathology[J]. Brain, 2016, 139(4):1265-1281. DOI:10.1093/brain/aww016 .
26	BAGLIETTO-VARGAS D, FORNER S, CAI L N, et al. Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology[J]. Nat Commun, 2021, 12:2421. DOI:10.1038/s41467-021-22624-z .
27	HUR J Y, FROST G R, WU X Z, et al. The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer's disease[J]. Nature, 2020, 586(7831):735-740. DOI:10.1038/s41586-020-2681-2 .
28	BALU D, KARSTENS A J, LOUKENAS E, et al. The role of APOE in transgenic mouse models of AD[J]. Neurosci Lett, 2019, 707:134285. DOI:10.1016/j.neulet.2019.134285 .
29	DUAN A R, JONASSON E M, ALBERICO E O, et al. Interactions between tau and different conformations of tubulin: implications for tau function and mechanism[J]. J Mol Biol, 2017, 429(9):1424-1438. DOI:10.1016/j.jmb.2017.03.018 .
30	GIACOBINI E, GOLD G. Alzheimer disease therapy—moving from amyloid-β to tau[J]. Nat Rev Neurol, 2013, 9(12):677-686. DOI:10.1038/nrneurol.2013.223 .
31	JOHNSON K A, SCHULTZ A, BETENSKY R A, et al. Tau positron emission tomographic imaging in aging and early Alzheimer disease[J]. Ann Neurol, 2016, 79(1):110-119. DOI:10.1002/ana.24546 .
32	LEWIS J, MCGOWAN E, ROCKWOOD J, et al. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein[J]. Nat Genet, 2000, 25(4):402-405. DOI:10.1038/78078 .
33	SAHARA N, LEWIS J, DETURE M, et al. Assembly of tau in transgenic animals expressing P301L tau: alteration of phosphorylation and solubility[J]. J Neurochem, 2002, 83(6):1498-1508. DOI:10.1046/j.1471-4159.2002.01241.x .
34	LEWIS J, DICKSON D W, LIN W L, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP[J]. Science, 2001, 293(5534):1487-1491. DOI:10.1126/science.1058189 .
35	D'ABRAMO C, ACKER C M, JIMENEZ H, et al. Passive immunization in JNPL3 transgenic mice using an array of phospho-tau specific antibodies[J]. PLoS One, 2015, 10(8): e0135774. DOI:10.1371/journal.pone.0135774 .
36	LAMBOURNE S L, HUMBY T, ISLES A R, et al. Impairments in impulse control in mice transgenic for the human FTDP-17 tau V337M mutation are exacerbated by age[J]. Hum Mol Genet, 2007, 16(14):1708-1719. DOI:10.1093/hmg/ddm119 .
37	TANEMURA K, MURAYAMA M, AKAGI T, et al. Neuro-degeneration with tau accumulation in a transgenic mouse expressing V337M human tau[J]. J Neurosci, 2002, 22(1):133-141. DOI:10.1523/jneurosci.22-01-00133.2002 .
38	SCHNÖDER L, GASPARONI G, NORDSTRÖM K, et al. Neuronal deficiency of p38α-MAPK ameliorates symptoms and pathology of APP or Tau-transgenic Alzheimer's mouse models[J]. FASEB J, 2020, 34(7):9628-9649. DOI:10.1096/fj. 201902731RR .
39	SAHARA N, VEGA I E, ISHIZAWA T, et al. Phosphorylated p38MAPK specific antibodies cross-react with sarkosyl-insoluble hyperphosphorylated tau proteins[J]. J Neurochem, 2004, 90(4):829-838. DOI:10.1111/j.1471-4159.2004.02558.x .
40	ODDO S, CACCAMO A, SHEPHERD J D, et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles[J]. Neuron, 2003, 39(3):409-421. DOI:10.1016/S0896-6273(03)00434-3 .
41	BILLINGS L M, ODDO S, GREEN K N, et al. Intraneuronal aβ causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice[J]. Neuron, 2005, 45(5):675-688. DOI:10.1016/j.neuron.2005.01.040 .
42	HUBER C M, YEE C, MAY T, et al. Cognitive decline in preclinical Alzheimer's disease: amyloid-beta versus tauopathy[J]. J Alzheimers Dis, 2018, 61(1):265-281. DOI:10. 3233/JAD-170490 .
43	ESCARTIN C, GALEA E, LAKATOS A, et al. Reactive astrocyte nomenclature, definitions, and future directions[J]. Nat Neurosci, 2021, 24(3):312-325. DOI:10.1038/s41593-020-00783-4 .
44	BELFIORE R, RODIN A, FERREIRA E, et al. Temporal and regional progression of Alzheimer's disease-like pathology in 3xTg-AD mice[J]. Aging Cell, 2019, 18(1): e12873. DOI:10.1111/acel.12873
45	LE DOUCE J, MAUGARD M, VERAN J, et al. Impairment of glycolysis-derived 1-serine production in astrocytes contributes to cognitive deﬁcits in Alzheimer's disease[J]. Cell Metab, 2020, 31(3):503-517. DOI:10.1016/j.cmet.2020. 02.004 .

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