Inflammation as a central mechanism in Alzheimer's disease

Jefferson W. Kinney1, Shane M. Bemiller2, Andrew S. Murtishaw1, Amanda M. Leisgang1, Arnold Salazar1, Bruce T. Lamb2
1Department of Psychology, University of Nevada, Las Vegas, Las Vegas, NV, USA
2Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA

Tóm tắt

AbstractAlzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by cognitive decline and the presence of two core pathologies, amyloid β plaques and neurofibrillary tangles. Over the last decade, the presence of a sustained immune response in the brain has emerged as a third core pathology in AD. The sustained activation of the brain's resident macrophages (microglia) and other immune cells has been demonstrated to exacerbate both amyloid and tau pathology and may serve as a link in the pathogenesis of the disorder. In the following review, we provide an overview of inflammation in AD and a detailed coverage of a number of microglia‐related signaling mechanisms that have been implicated in AD. Additional information on microglia signaling and a number of cytokines in AD are also reviewed. We also review the potential connection of risk factors for AD and how they may be related to inflammatory mechanisms.

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Tài liệu tham khảo

Prince M., 2016, World Alzheimer Report 2016: Improving Healthcare for People Living With Dementia: Coverage, Quality and Costs Now and in the Future

10.1212/WNL.0b013e31828726f5

Alzheimer's Impact Movement, 2017, Alzheimer's Disease Caregivers Factsheet

10.1146/annurev.ne.17.030194.002421

10.1146/annurev-neuro-061010-113613

10.1111/j.1471-4159.1992.tb10128.x

10.1006/nbdi.2000.0321

10.1073/pnas.90.5.2092

Butterfield D.A., 2012, Amyloid β‐Peptide (1–42)‐Induced oxidative stress in Alzheimer disease: Importance in disease pathogenesis and progression, Antioxid Redox Signal, 19, 823, 10.1089/ars.2012.5027

10.1038/359322a0

10.1074/jbc.M402034200

10.3233/JAD-2010-1221

10.1159/000369101

10.1016/0166-2236(93)90008-A

10.1126/science.1439760

10.1007/s00018-008-8271-3

10.1097/00005072-199908000-00001

10.1038/nm0796-783

10.1073/pnas.91.12.5562

10.1073/pnas.94.1.298

10.1016/0006-8993(89)91396-6

10.1016/S0079-6123(08)64021-2

10.1016/S0140-6736(86)92134-3

10.2174/156720510793611592

10.1016/S0021-9258(20)80536-5

10.1016/0006-8993(77)90155-X

10.1073/pnas.72.5.1858

10.1152/physrev.00024.2003

10.1083/jcb.143.3.777

10.2174/092986708785909111

10.1007/s00401-017-1707-9

10.4161/pri.1.1.4055

Šimić G., 2016, Tau Protein Hyperphosphorylation and aggregation in Alzheimer's disease and other tauopathies, and possible neuroprotective strategies, Biomolecules, 6, 10.3390/biom6010006

10.1186/s13195-016-0207-9

10.1126/science.1072994

Morris G.P., 2014, Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer's disease, Acta Neuropathol Commun, 2

10.1001/archneur.60.5.729

10.1097/NEN.0b013e31825018f7

10.1097/NEN.0b013e3181919a48

10.1074/jbc.275.11.7918

10.1016/S0197-4580(00)00124-X

10.1523/JNEUROSCI.20-02-00558.2000

10.1073/pnas.86.19.7611

10.1097/00005072-199503000-00014

10.1017/S0317167100029863

10.1016/0165-0173(95)00011-9

10.1097/nen.0b013e31812503e1

10.1016/0046-8177(95)90001-2

10.1016/j.biocel.2004.07.009

10.1002/pnp.444

10.1186/1742-2094-9-179

Gomez‐Nicola D., 2015, Post‐mortem analysis of neuroinflammatory changes in human Alzheimer's disease, Alzheimers Res Ther, 7, 10.1186/s13195-015-0126-1

10.1016/j.neurobiolaging.2012.09.012

10.1016/j.bbadis.2015.11.011

10.1016/j.pnpbp.2017.05.007

10.1007/s00702-017-1731-x

10.1186/1742-2094-11-120

10.1016/j.jalz.2013.12.010

10.1186/1742-2094-8-26

Meraz‐Ríos M.A., 2013, Inflammatory process in Alzheimer's Disease, Front Integr Neurosci, 7

Rubio‐Perez J.M., 2012, A Review: Inflammatory process in Alzheimer's disease, role of cytokines, ScientificWorldJournal, 2012

Herrero M.‐T., 2015, Inflammation in Parkinson's disease: role of glucocorticoids, Front Neuroanat, 9

10.1186/s40035-015-0042-0

10.1016/j.it.2015.04.007

Ellrichmann G., 2013, The role of the immune system in Huntington's disease, Clin Dev Immunol, 2013, 10.1155/2013/541259

Silajdžić E., 2013, A critical evaluation of inflammatory markers in Huntington's Disease plasma, J Huntington's Dis, 2, 125, 10.3233/JHD-130049

Breunig J., 2013, Brain injury, neuroinflammation and Alzheimer's disease, Front Aging Neurosci, 5, 10.3389/fnagi.2013.00026

10.1007/s13311-014-0319-5

10.1016/j.mcn.2015.03.012

10.2174/156652411795243450

10.3892/mmr.2016.4948

10.1111/imm.12233

10.1111/j.1365-2567.2009.03225.x

Cappellano G., 2013, Immunity and inflammation in neurodegenerative diseases, Am J Neurodegenerative Dis, 2, 89

10.1016/j.cell.2010.02.016

10.1093/ajcn/83.2.470S

10.1073/pnas.162350199

10.1038/cddis.2011.50

10.1523/JNEUROSCI.2868-05.2005

10.1196/annals.1332.006

10.1523/JNEUROSCI.1071-09.2009

10.1007/s00401-014-1371-2

10.1073/pnas.0905529106

10.1016/S0197-4580(88)80079-4

10.4065/73.10.951

10.1212/WNL.44.2.227

10.1212/WNL.45.1.51

10.1016/j.neurobiolaging.2006.03.013

10.1007/s40266-015-0239-z

10.1212/WNL.42.2.447

10.1186/alzrt24

10.1038/emm.2006.40

10.1073/pnas.86.19.7606

10.1212/WNL.55.8.1158

10.1016/j.yexcr.2004.01.002

Sarma J.D., 2014, Microglia‐mediated neuroinflammation is an amplifier of virus‐induced neuropathology, J NeuroVirology, 20, 122, 10.1007/s13365-013-0188-4

10.1016/0361-9230(89)90018-X

Glenn J.A., 1992, Characterisation of ramified microglial cells: detailed morphology, morphological plasticity and proliferative capability, J Anat, 180, 109

10.1038/nn1472

10.1007/s11481-013-9434-z

10.1016/0306-4522(96)00106-6

10.1074/jbc.R115.637157

10.1016/j.tins.2007.07.007

10.1002/(SICI)1097-4547(19990101)55:1<17::AID-JNR3>3.0.CO;2-J

10.1016/S0165-5728(03)00009-2

10.1002/jnr.10253

10.1073/pnas.95.18.10896

10.1523/JNEUROSCI.4814-07.2008

10.1002/cne.902110407

10.1016/0304-3940(88)90585-X

Mrak R.E., 2012, Microglia in Alzheimer Brain: A neuropathological perspective, Int J Alzheimer's Dis

10.1002/glia.23074

10.1016/S0002-9440(10)65423-5

10.1038/78682

10.1016/j.neuron.2006.01.022

10.1074/jbc.M110.149468

10.1074/jbc.M111.324616

10.1523/JNEUROSCI.0616-08.2008

10.1096/fj.09-141754

10.1172/JCI31450

10.1038/374647a0

10.1097/00005072-199807000-00008

10.1371/journal.pone.0060921

10.1016/j.jneuroim.2009.02.003

Bhaskar K., 2014, Microglial derived tumor necrosis factor‐α drives Alzheimer's disease‐related neuronal cell cycle events, Neurobiol Dis, 62, 10.1016/j.nbd.2013.10.007

10.1016/j.brainresbull.2011.10.004

10.1046/j.1471-4159.2000.0741017.x

10.1002/ana.410100605

10.1084/jem.20142322

Bemiller S.M., 2017, TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy, Mol Neurodegener, 12, 10.1186/s13024-017-0216-6

10.1523/JNEUROSCI.4586-14.2015

10.1016/j.cell.2015.01.049

10.1056/NEJMoa1211851

10.1016/j.bcp.2013.11.021

Jin S.C., 2015, TREM2 is associated with increased risk for Alzheimer's disease in African Americans, Mol Neurodegener, 10

10.1056/NEJMoa1211103

10.1084/jem.20030027

10.1086/342259

10.1038/77153

10.1111/j.1440-1789.2010.01127.x

10.1212/WNL.33.1.81

10.1111/j.1460-9568.2004.03729.x

10.1212/WNL.43.8.1467

10.1126/science.8346443

Ulrich J.D., 2014, Altered microglial response to A beta plaques in APPPS1‐21 mice heterozygous for TREM2, Mol Neurodegener, 9, 10.1186/1750-1326-9-20

10.1523/JNEUROSCI.2110-16.2016

10.3233/JAD-161277

10.1038/nn.4126

10.3233/JAD-130854

10.1186/1750-1326-9-20

10.1084/jem.20151948

10.1016/j.neuron.2016.05.003

10.1007/s00401-015-1388-1

10.1172/JCI77983

10.1016/j.cell.2017.07.023

10.1186/s13024-017-0216-6

10.1073/pnas.1710311114

10.1016/j.cell.2017.05.018

10.1038/385640a0

10.1016/S1471-4906(01)02051-8

10.1098/rsob.130181

10.1182/blood-2008-07-170787

10.1172/JCI71307

10.4049/jimmunol.1300090

10.1038/nn1715

Fuhrmann M., 2010, Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease, Nat Publishing Group, 13, 411

10.2353/ajpath.2010.100265

10.1038/nn.3554

10.1016/S0014-5793(98)00583-3

10.1016/S0092-8674(00)80438-9

10.3389/fncel.2014.00229

10.1002/(SICI)1098-1136(20000215)29:4<305::AID-GLIA2>3.0.CO;2-V

10.1016/S0006-8993(03)02867-1

10.1128/MCB.20.11.4106-4114.2000

10.1016/j.neuron.2010.08.023

10.1016/j.neurobiolaging.2013.06.007

10.1016/j.neulet.2008.03.019

10.1074/jbc.M111.254268

10.1016/S1054-3589(10)58006-2

10.1016/j.cell.2015.12.056

10.1038/nm.3639

10.5607/en.2017.26.3.122

Li Y., 2016, Implications of GABAergic Neurotransmission in Alzheimer's disease, Front Aging Neurosci, 8

10.1038/ncomms5159

10.1016/j.neubiorev.2016.01.007

10.1002/glia.21087

10.1016/j.mcn.2003.10.023

10.1016/j.cnr.2006.09.004

10.1111/bph.13125

10.1113/jphysiol.2014.278754

Le Meur K., 2012, GABA release by hippocampal astrocytes, Front Comput Neurosci, 6, 10.3389/fncom.2012.00059

10.1016/0304-3940(91)90490-K

10.1016/S0197-4580(01)00291-3

10.3233/JAD-2009-0976

10.1523/JNEUROSCI.4580-03.2004

10.1083/jcb.200705042

10.1016/j.neurobiolaging.2008.10.012

Chang R., 2017, Tumor necrosis factor α Inhibition for Alzheimer's Disease, J Cent Nervous Syst Dis, 9

10.1523/JNEUROSCI.21-04-01179.2001

10.2353/ajpath.2007.060378

10.1002/jnr.20266

10.1159/000255051

10.1016/j.brainresrev.2008.07.003

Cacabelos R., 1994, Brain interleukin‐1 beta in Alzheimer's disease and vascular dementia, Methods Findings Exp Clin Pharmacol, 16, 141

Farrar W.L., 1987, Visualization and characterization of interleukin 1 receptors in brain, J Immunol, 139, 459, 10.4049/jimmunol.139.2.459

10.1073/pnas.89.21.10075

10.1016/S0024-3205(97)00936-3

10.1038/42257

10.1016/j.bbamcr.2011.01.034

10.1016/j.bbamcr.2016.03.018

10.1212/WNL.0000000000000665

10.1016/0304-3940(95)12192-7

10.1016/j.jneuroim.2015.04.014

10.1007/s00406-004-0558-2

10.1007/BF00571510

10.1016/S0169-328X(97)00356-2

10.1038/sj.onc.1209943

10.1073/pnas.94.6.2642

10.1096/fj.03-1378fje

10.1016/S0968-0896(02)00440-6

10.1172/JCI18162

10.1016/S0002-9440(10)63269-5

10.1016/S0165-5728(00)00404-5

10.1159/000474940

10.1016/j.neuron.2015.01.021

10.1016/j.neuron.2014.12.068

10.1038/sj.gene.6363964

10.1016/j.jns.2010.12.005

Chao C.C., 1994, Transforming growth factor beta in Alzheimer's disease, Clin Diagn Lab Immunol, 1, 109, 10.1128/cdli.1.1.109-110.1994

10.1016/S0002-9440(10)61105-4

10.1016/S0197-0186(01)00046-8

10.1007/s00441-011-1230-6

10.1007/s12603-010-0325-1

10.1016/j.exger.2004.07.007

10.1523/JNEUROSCI.3351-16.2017

10.1093/aje/kwf074

10.1136/bmj.322.7300.1447

10.1093/ije/20.Supplement_2.S28

10.1136/jnnp.74.7.857

Thakur M.K., 2012, Traumatic brain injury: A risk factor of Alzheimer's disease, Neurosci Biobehav Rev, 36, 1376, 10.1016/j.neubiorev.2012.02.013

Djordievic J., 2016, Traumatic brain injury as a risk factor for Alzheimer's disease: is inflammatory signaling a key player?, Curr Alzheimer Res, 13, 730, 10.2174/1567205013666160222110320

10.1007/s00259-005-1762-7

10.1016/j.nut.2010.07.021

10.1016/j.pneurobio.2013.06.004

10.2337/diabetes.53.2.474

10.1016/S1474-4422(05)70284-2

10.1016/j.ejphar.2008.02.049

10.1212/WNL.53.9.1937

10.1212/WNL.0b013e31822f0435

10.1371/journal.pone.0087095

10.1001/archneur.63.11.1551

10.1159/000324134

10.1172/JCI104130

Bonadonna R.C., 1991, Glucose metabolism in obesity and type 2 diabetes, Diabete & Metabolisme, 17, 112

10.3233/JAD-2005-8304

10.3233/JAD-2005-7107

Monte de S.M., 2001, Ethanol impairs insulin‐stimulated mitochondrial function in cerebellar granule neurons, Cell Mol Life Sci, 58, 1950, 10.1007/PL00000829

10.3233/JAD-2006-9102

10.1073/pnas.0809158106

Li W., 2017, Type 2 diabetes mellitus and cerebrospinal fluid Alzheimer's disease biomarker Aβ1‐42 in Alzheimer's Disease Neuroimaging Initiative participants, Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 10, 94, 10.1016/j.dadm.2017.11.002

10.1126/science.7678183

10.1038/oby.2000.86

10.1161/01.ATV.0000248096.62495.73

10.1080/13813450802181047

10.1016/j.imlet.2008.02.002

10.1001/archneurol.2011.670

10.1016/j.biopsych.2010.06.012

10.1016/0165-5728(93)90027-V

10.1159/000097202

10.1016/j.physbeh.2012.05.015

Freeman L.R., 2011, Vascular changes in rat hippocampus following a high saturated fat and cholesterol diet, J Cereb Blood Flow Metab, 32, 643, 10.1038/jcbfm.2011.168

10.1093/gerona/glt177

Perry V.H., 2014, Microglial priming in neurodegenerative disease, Nat Publishing Group, 10, 217

10.1186/s12974-015-0467-5

Ledo J.H., 2016, Cross talk between brain innate immunity and serotonin signaling underlies depressive‐like behavior induced by Alzheimer's amyloid‐ oligomers in mice, J Neurosci, 36, 12106, 10.1523/JNEUROSCI.1269-16.2016

10.1038/nrneurol.2012.263

10.1007/s12264-013-1422-z

10.1001/jama.1997.03550160069041

10.1016/j.immuni.2017.08.008

10.1001/jama.282.1.40