Abstract
Amyloid plaques and neurofibrillary tangles are two main characteristics of Alzheimer’s disease (AD). As cerebral resident phagocytes, microglia have different roles in Aβ pathology and tau pathology. In this review, we discuss microglial functions in the formation, clearance, and spread of Aβ and tau. Many receptors and enzymes, which are related to microglia, participate in AD pathologies and thus are thought to be potential targets of AD. So, making use of microglia can be beneficial to confine AD pathologies. To sum up, this article review the roles of microglia in AD pathology and possible corresponding treatments.
[http://dx.doi.org/10.1016/S2468-2667(21)00249-8] [PMID: 34998485]
[http://dx.doi.org/10.1073/pnas.90.16.7789] [PMID: 8356085]
[http://dx.doi.org/10.1016/S0014-5793(99)01279-X] [PMID: 10526177]
[http://dx.doi.org/10.1002/glia.23510] [PMID: 30417428]
[http://dx.doi.org/10.1146/annurev-immunol-093019-110159] [PMID: 33556248]
[http://dx.doi.org/10.1111/nan.12011] [PMID: 23252647]
[http://dx.doi.org/10.1038/s41593-018-0242-x] [PMID: 30258234]
[http://dx.doi.org/10.1111/jnc.13607] [PMID: 26990767]
[http://dx.doi.org/10.3389/fnagi.2022.827263] [PMID: 35663580]
[http://dx.doi.org/10.1016/j.immuni.2017.08.008] [PMID: 28930663]
[http://dx.doi.org/10.1093/brain/awy188] [PMID: 30052812]
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.07.024] [PMID: 25169677]
[http://dx.doi.org/10.1038/s41467-019-11674-z] [PMID: 31434879]
[http://dx.doi.org/10.1002/glia.23074] [PMID: 27658617]
[http://dx.doi.org/10.1038/nature25158] [PMID: 29293211]
[http://dx.doi.org/10.1038/ncomms7176] [PMID: 25630253]
[http://dx.doi.org/10.1016/j.neuron.2016.05.003] [PMID: 27196974]
[http://dx.doi.org/10.1084/jem.20151948] [PMID: 27091843]
[http://dx.doi.org/10.3390/biom11030434] [PMID: 33804246]
[http://dx.doi.org/10.1038/s41467-021-23111-1] [PMID: 34021136]
[http://dx.doi.org/10.1523/JNEUROSCI.0616-08.2008] [PMID: 18701698]
[http://dx.doi.org/10.1038/s41590-021-00913-5] [PMID: 33859405]
[http://dx.doi.org/10.1084/jem.20041611] [PMID: 15728241]
[http://dx.doi.org/10.1016/j.neuron.2016.06.015] [PMID: 27477018]
[http://dx.doi.org/10.1038/npp.2014.164] [PMID: 25047746]
[http://dx.doi.org/10.1016/j.neuron.2018.02.002] [PMID: 29518357]
[http://dx.doi.org/10.1016/j.neuron.2018.01.031] [PMID: 29518356]
[http://dx.doi.org/10.1038/s41598-017-11634-x] [PMID: 28894284]
[http://dx.doi.org/10.1016/j.neuron.2013.06.046] [PMID: 24012002]
[http://dx.doi.org/10.15252/emmm.202012308] [PMID: 32790063]
[http://dx.doi.org/10.1038/s41467-019-09118-9] [PMID: 30911003]
[http://dx.doi.org/10.1002/glia.22331] [PMID: 22438044]
[http://dx.doi.org/10.1523/JNEUROSCI.0829-08.2008] [PMID: 18562603]
[http://dx.doi.org/10.1093/brain/awh531] [PMID: 15857927]
[http://dx.doi.org/10.1016/j.nbd.2011.01.005] [PMID: 21220023]
[http://dx.doi.org/10.1523/JNEUROSCI.1569-12.2012] [PMID: 23197723]
[http://dx.doi.org/10.3233/JAD-141227] [PMID: 25079809]
[http://dx.doi.org/10.1016/j.neuron.2013.04.014] [PMID: 23623698]
[http://dx.doi.org/10.1038/s41586-019-1088-4] [PMID: 30944478]
[http://dx.doi.org/10.3233/JAD-2011-101014] [PMID: 21403390]
[http://dx.doi.org/10.1186/s12974-018-1250-1] [PMID: 30029608]
[http://dx.doi.org/10.1186/s12974-016-0522-x] [PMID: 26939570]
[http://dx.doi.org/10.1093/brain/awl249] [PMID: 16984903]
[http://dx.doi.org/10.4049/jimmunol.1101121] [PMID: 22198949]
[http://dx.doi.org/10.2353/ajpath.2009.090418] [PMID: 19834064]
[http://dx.doi.org/10.1080/15548627.2018.1556946] [PMID: 30523761]
[http://dx.doi.org/10.3233/JAD-180904] [PMID: 30775984]
[http://dx.doi.org/10.1111/j.1471-4159.2012.07700.x] [PMID: 22353164]
[http://dx.doi.org/10.1128/MCB.00544-13] [PMID: 24001770]
[http://dx.doi.org/10.1016/j.neuroscience.2020.07.020] [PMID: 32697980]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.016080] [PMID: 26503748]
[http://dx.doi.org/10.3233/JAD-160456] [PMID: 27472885]
[http://dx.doi.org/10.1074/jbc.M110.142356] [PMID: 20947502]
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.10.021] [PMID: 29175709]
[http://dx.doi.org/10.1523/JNEUROSCI.5268-11.2012] [PMID: 22836247]
[http://dx.doi.org/10.2353/ajpath.2009.090147] [PMID: 19893026]
[http://dx.doi.org/10.1172/JCI66541] [PMID: 24487585]
[http://dx.doi.org/10.1074/jbc.273.49.32730] [PMID: 9830016]
[http://dx.doi.org/10.1002/jnr.490420307] [PMID: 8583501]
[http://dx.doi.org/10.1016/S0304-3940(03)00898-X] [PMID: 12972166]
[http://dx.doi.org/10.3390/cells9102277] [PMID: 33065974]
[http://dx.doi.org/10.3389/fimmu.2019.02780] [PMID: 31849963]
[http://dx.doi.org/10.1186/s12974-015-0411-8] [PMID: 26538310]
[http://dx.doi.org/10.3389/fimmu.2020.582998] [PMID: 33519806]
[http://dx.doi.org/10.1016/j.neuron.2014.12.068] [PMID: 25619654]
[http://dx.doi.org/10.1016/j.neuron.2014.11.020] [PMID: 25619653]
[http://dx.doi.org/10.1038/s41586-021-03734-6] [PMID: 34262178]
[http://dx.doi.org/10.1523/JNEUROSCI.2117-15.2016] [PMID: 26758846]
[http://dx.doi.org/10.1016/S0304-3940(03)00474-9] [PMID: 12812836]
[http://dx.doi.org/10.1016/j.neuroscience.2020.05.004] [PMID: 32522344]
[http://dx.doi.org/10.1186/1750-1326-2-2] [PMID: 17241462]
[http://dx.doi.org/10.1016/j.prostaglandins.2013.09.002] [PMID: 24076168]
[http://dx.doi.org/10.1007/s11064-017-2284-y] [PMID: 28466190]
[http://dx.doi.org/10.1007/s00401-019-02013-z] [PMID: 31006066]
[http://dx.doi.org/10.1186/s13195-020-00688-1] [PMID: 33008458]
[http://dx.doi.org/10.1007/s11064-020-03121-z] [PMID: 32929691]
[http://dx.doi.org/10.1016/j.bbi.2016.12.014] [PMID: 28003153]
[http://dx.doi.org/10.1016/j.celrep.2020.02.025] [PMID: 32187546]
[http://dx.doi.org/10.1111/jcmm.16098] [PMID: 33225628]
[http://dx.doi.org/10.1016/j.brainres.2016.08.016] [PMID: 27531183]
[http://dx.doi.org/10.1021/acschemneuro.8b00029] [PMID: 29543435]
[http://dx.doi.org/10.1021/acs.jproteome.0c00934] [PMID: 33534581]
[http://dx.doi.org/10.3233/JAD-150704] [PMID: 26638867]
[http://dx.doi.org/10.1016/j.jneuroim.2009.01.013] [PMID: 19232747]
[http://dx.doi.org/10.1016/j.neuron.2018.10.031] [PMID: 30415998]
[http://dx.doi.org/10.1096/fj.08-123877] [PMID: 19289607]
[http://dx.doi.org/10.1016/j.neuron.2010.08.023] [PMID: 20920788]
[http://dx.doi.org/10.1093/brain/awv081] [PMID: 25833819]
[http://dx.doi.org/10.1186/s13024-017-0200-1] [PMID: 28810892]
[http://dx.doi.org/10.1007/s00401-013-1111-z] [PMID: 23589030]
[http://dx.doi.org/10.1007/s00401-020-02125-x] [PMID: 31925534]
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.08.019] [PMID: 26364736]
[http://dx.doi.org/10.1186/s13024-017-0216-6] [PMID: 29037207]
[http://dx.doi.org/10.1073/pnas.1710311114] [PMID: 29073081]
[http://dx.doi.org/10.1073/pnas.1811411115] [PMID: 30232263]
[http://dx.doi.org/10.1073/pnas.2023418118]
[http://dx.doi.org/10.1016/j.cell.2019.05.056] [PMID: 31257024]
[http://dx.doi.org/10.1038/srep11161] [PMID: 26057852]
[http://dx.doi.org/10.1038/s41586-018-0543-y] [PMID: 30232451]
[http://dx.doi.org/10.1038/s41598-019-41105-4] [PMID: 30874605]
[http://dx.doi.org/10.1016/j.celrep.2016.06.099] [PMID: 27475227]
[http://dx.doi.org/10.1186/s12974-019-1694-y] [PMID: 31915009]
[http://dx.doi.org/10.1186/s12974-014-0161-z] [PMID: 25217135]
[http://dx.doi.org/10.1186/s12974-018-1309-z] [PMID: 30227881]
[http://dx.doi.org/10.1038/nn.4132] [PMID: 26436904]
[http://dx.doi.org/10.1038/s41598-019-45676-0] [PMID: 31263146]
[http://dx.doi.org/10.1186/s13024-020-00396-2] [PMID: 32811520]
[http://dx.doi.org/10.1038/s41380-018-0258-3] [PMID: 30283031]
[http://dx.doi.org/10.1186/s13024-021-00440-9] [PMID: 33752701]
[http://dx.doi.org/10.1016/j.neuron.2021.02.010] [PMID: 33675684]
[http://dx.doi.org/10.1084/jem.20210542] [PMID: 34100905]
[http://dx.doi.org/10.1038/s41593-019-0433-0] [PMID: 31235932]
[http://dx.doi.org/10.1016/j.neuroscience.2020.09.024] [PMID: 32941933]
[http://dx.doi.org/10.1038/nature11729] [PMID: 23254930]
[http://dx.doi.org/10.1038/s41586-019-1769-z] [PMID: 31748742]
[http://dx.doi.org/10.3233/JAD-200219] [PMID: 32741816]
[http://dx.doi.org/10.1111/j.1749-6632.2009.04607.x] [PMID: 19796238]
[http://dx.doi.org/10.1155/2021/7834421] [PMID: 34512767]
[http://dx.doi.org/10.1016/j.neulet.2008.11.059] [PMID: 19084047]
[http://dx.doi.org/10.1002/stem.1125] [PMID: 22570192]
[http://dx.doi.org/10.3233/JAD-190974] [PMID: 31796681]
[http://dx.doi.org/10.1001/archneurol.2011.1538] [PMID: 21987394]
[http://dx.doi.org/10.1038/nature19323] [PMID: 27582220]
[http://dx.doi.org/10.1186/alzrt246] [PMID: 25031633]
[http://dx.doi.org/10.1186/s13195-018-0447-y] [PMID: 30486882]
[http://dx.doi.org/10.1002/prot.25978] [PMID: 32666627]
[http://dx.doi.org/10.1016/j.nbd.2020.105010] [PMID: 32682954]
[http://dx.doi.org/10.15252/emmm.201606370] [PMID: 27402340]
[http://dx.doi.org/10.1126/scitranslmed.abb2639] [PMID: 33980574]
[http://dx.doi.org/10.1016/j.nbd.2020.105120] [PMID: 32991997]
[PMID: 30569088]
[http://dx.doi.org/10.1136/bmj.n1682] [PMID: 34226181]
[http://dx.doi.org/10.1038/s41591-021-01369-8] [PMID: 34155411]
[http://dx.doi.org/10.1001/jamaneurol.2022.1375] [PMID: 35696185]
[http://dx.doi.org/10.1016/S0140-6736(22)02480-1] [PMID: 36463893]
[http://dx.doi.org/10.1007/s13311-022-01308-6] [PMID: 36253511]
[http://dx.doi.org/10.1126/sciadv.aau6328] [PMID: 30820451]
[http://dx.doi.org/10.1073/pnas.1916318116] [PMID: 31685616]
[http://dx.doi.org/10.1038/s41598-018-19641-2] [PMID: 29348604]
[http://dx.doi.org/10.3389/fncel.2022.894601] [PMID: 35677758]
[http://dx.doi.org/10.1016/j.bbi.2020.07.041] [PMID: 32739363]
[http://dx.doi.org/10.1084/jem.20200785] [PMID: 32579671]
[http://dx.doi.org/10.1186/1750-1326-9-20] [PMID: 24893973]