1,470
Views
66
CrossRef citations to date
0
Altmetric
Review

Targeting microglia for the treatment of Alzheimer’s disease

&

Bibliography

  • Del Rio Hortega P. El ‘tercer elemento’ de los centros nerviosos Poder fagocitario y movilidad de la micolia. Bol Soc Exp Biol Ano 1919;ix:154-66
  • Penfield W. Microglia and the process of phagocytosis in gliomas. Am J Pathol 1925;1:77-83
  • van Furth R. Current view on the mononuclear phagocyte system. Immunobiology 1982;1611:78-85
  • McGeer PL, Itagaki S, McGeer EG. Expression of the histocompatability glycoprotein in neurological disease. Neurobiol Aging 1988;243:91-5
  • Luber-Narod J, Rogers J. Immune system associated antigens expressed by cells of the human central nervous system. Neurosci Lett 1988;942:65-73
  • McGeer PL, McGeer EG. Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci 2004;1035:104-16
  • Prokop S, Miller KR, Heppner FL. Microglia actions in Alzheimer’s disease. Acta Neuropathol 2013;126:461-77
  • Barkers CF, Billingham RE. Immunologically privileged sites. Adv Immunol 1977;2:51-4
  • Rogers J, Webster S, Schultz J, et al. Complement activation by b-amyloid in Alzheimer disease. Proc Natl Acad Sci USA 1992;89:1016-20
  • Morales I, Jimenez JM, Mancilla M, Maccionii RB. Tau oligomers and fibrils induce activation of microglial cells. J Alzheimers Dis 2013;37:849-56
  • Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996;19:312-18
  • Moore AH, Bigbee MJ, Boynton GE, et al. Non-steroidal anti-inflammatory drugs in Alzheimer’s disease, and Parkinson’s disease: reconsidering the role of neuroinflammation. Pharmaceuticals 2010;51:812-41
  • McGeer EG, McGeer PL. Aging, neurodegenerative disease, and the brain. Can J Aging 1997;1662:18-36
  • Bora PS, Sohn J-H, Cruz JM, et al. Role of complement and complement membrane attack complex in laser-induced choroidal neovascularization. J Immunol 2005;174:491-7
  • Bowes Rickman C, Farsiu S, Toth CA, Klingeborn M. Dry age-related macular degeneration: mechanisms, therapeutic targets and imaging. Invest Ophthalmol Vis Sci 2013;54(14):ORSF68-80
  • Lee M, McGeer EG, McGeer PL. Activated human microglia stimulate neuroblastoma cells to upregulate production of beta-amyloid protein; implications for Alzheimer disease pathology. Neurobiol Aging 2014. Available from: http://dx.doi.org/10.1016/j.neurobiolaging.2014.07.024
  • Kaushik DK, Basu A. A friend in need may not be a friend indeed: role of microglia in neurodegenerative diseases. CNS Neurol Disord Drug Targets 2013;12:726-40
  • Morales I, Guzman-Martinez L, Cerda-Troncoso C, et al. Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci 2014;8:112
  • Hensley K. Neuroinflammation in Alzheimer’s disease: mechanisms, pathologic consequences, and potential for therapeutic manipulation. J Alzheimer Dis 2010;21:1-14
  • Mosher KI, Wyss-Coray T. Microglial dysfunction in brain aging and Alzheimer’s disease. Biochem Pharmacol 2014;88:594-604
  • McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiological studies. Neurology 1996;147:425-32
  • McGeer EG, McGeer PL. Inflammatory processes in Alzheimer’s disease. Prog NeuroPsychopharmacol Biol Psychiatry 2003;27:741-9
  • Mackenzie IR, Munoz DG. Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology 1998;50:986-90
  • Rogers J, Webster S, Schultz J, et al. Clinical trial of indomethacin in Alzheimer’s disease. Neurology 1993;431:609-11
  • Scharf S, Mander A, Ugoni A, et al. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer’s disease. Neurology 1999;531:97-201
  • Arai H, Suzuki K, Sasaki H, et al. A new interventional strategy for Alzheimer’s disease by Japanese herbal medicine. Nihon Ronen Igakkai Zasshi 2000;37:212-15
  • Sainali SM, Inram DM, Talwaker S, et al. Results of a double-blind, placebo-controlled study 6f celecoxib for the progression of Alzheimer’s disease. 6th International Stockholm-Springfield Symposium on Advances in Alzheimer Therapy; 2000. 189
  • Martin BK, Szekely C, Brandt J, et al. Cognitive function over time in the Alzheimer’s disease anti-inflammatory prevention trial (ADAPT): results of a randomized controlled trial of naproxen and celecoxib. Arch Neurol 2008;6:896-905
  • Breitner JC, Baker LD, Montine TJ, et al. Extended results of the Alzheimer’s disease anti-inflammatory prevention trial (ADAPT). Alzheimers Dement 2011;7(4):402-11
  • Aisen PS, Schmeidler J, Pasinetti G. Randomized pilot study of nimesulide in Alzheimer’s disease. Neurology 2002;581:50-4
  • Yasojima K, Schwab C, McGeer EG, McGeer PL. Distribution of cyclooxogenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs. Brain Res 1999;830:226-36
  • Lee M, Guo J-P, Schwab C, et al. Selective inhibition of the membrane attack complex of complement by low molecular weight components of the aurin tricarboxylic acid synthetic complex. Neurobiol Aging 2012;33:2237-46
  • Lee M, Guo J-P, McGeer EG, McGeer PL. Aurin tricarboxylic acid self-protects by inhibiting aberrant complement activation at the C3 convertase and C9 binding stages. Neurobiol Aging 2013;34:1451-61
  • Lastres-Becker I, Innamorato NG, Jaworski T, et al. Fractalkine activates NRF2/NFE2L2 and hemoxygenase 1 to restrain tauopathy-induced microgliosis. Brain 2014;137:78-91
  • Lee M, Schwab C, McGeer PL. Astrocytes are GABAergic cells that modulate microglial activity. Glia 2013;59:152-6
  • Schwab C, Yu S, Wong W, et al. GAD65, GAD67 and GABAT immunostaining in human brain and apparent GAD65 loss in Alzheimer’s disease. J Alzheimers Dis 2013;33:1073-88
  • Olsson B, Haute J, Lautner R, et al. Microglial markers are elevated in the prodromal phase of Alzheimer’s disease and vascular dementia. J Alzheimers Dis 2013;33:45-53
  • Guo J-P, Yu S, McGeer PL. Simple in vitro assays to identify amyloid-b aggregation blockers for Alzheimer’s disease therapy. J Alzheimers Dis 2010;19:1359-70
  • Baron R, Babcock AA, Nemirovsky A, et al. Accelerated microglial pathology is associated with Ab in mouse models of Alzheimer’s disease. Aging Cell 2014;13(4):584-95
  • Minoque AM, Jones RS, Kelly RJ, et al. Age-associated dysregulation of microglial activation is coupled with enhanced blood-brain barrier permeability and pathology in APP/PS1 mice. Neurobiol Aging 2014;341:442-52
  • Cavanagh C, Colby-Miller J, Bouvier D, et al. Beta CTF-correlated burst of hippocampal TNF-a occurs at a very early, pre-plaque stage in the TgCRND8 mouse model of Alzheimer’s disease. J Alzhemiers Dis 2013;362:33-8
  • Wright AL, Zinn R, Hohensinn B, et al. Neuroinflammation and neuronal loss precede Ab plaque deposition in the hAPP-J20 mouse model of Alzheimer’s disease. PLoS One 2013;8(4):e59586
  • Hanzel CE, Pichet-Binette A, Pimental LS, et al. Neuronal driven pre-plaque inflammation in a transgenic rat model of Alzheimer’s disease. Neurobiol Aging 2014;35(10):2249-62
  • Woodling NS, Wang Q, Priyam PG, et al. Suppression of Alzheimer-associated inflammation by microglial prostaglandin-E2 EP4 receptor signaling. J Neurosci 2014;34:5882-94
  • Mandrekar-Colucci S, Karlo JC, Landreth GE. Mechanisms underlying the rapid peroxisome proliferators-activated receptor-g −mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer’s disease. J Neurosci 2012;32:10117-28
  • Yamanaka M, Ishokawa T, Griep A, et al. PPARg/RXRa-induced and CD36-mediated microglial amyloid-b phagocytosis results in cognitive improvement in amyloid precursor protein/presenilin 1 mice. J Neurosci 2012;32:17321-31
  • Richard KL, Filali M, Prefontaine P, Rivest S. Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid b1-42 and delay the cognitive decline in a mouse model of Alzheimer’s disease. J Neurosci 2008;28:5784-93
  • Zhuang J, Zhan H, Zhou R, et al. Regulation of prostaglandin F2a against b-amyloid clearance and its inflammation induction through LXR/RXR heterodimer antagonism in microglia. Prostaglandins Other Lipid Mediat 2013;106:45-52
  • Tichauer JE, von Bernhardi R. Transforming growth factor-b stimulates b amyloid uptake by microglia through Smad3-dependent mechanisms. J Neurosci Res 2012;90:1970-80
  • Ma Y, Bao J, Shen H, et al. Activated cyclin-dependent kinase 5 promotes microglial phagocytosis of fibrillar b–amyloid by up-regulating lipoprotein lipase expression. Mol Cell Proteomics 2013;12:2833-4
  • Zhu Y, Hou H, Rezai-Zadeh K, et al. CD45 deficiency drives amyloid-b peptide oligomers and neuroal loss in Alzheimer’s disease mice. J Neurosci 2011;31:1355-65
  • El Khoury J, Toft M, Hickman SE, et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 2007;13:432-7
  • Simard AR, Soulet D, Gowing G, et al. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 2006;49:489-502
  • Yan SD, Chen X, Fu J, et al. RAGE and amyloid-b peptide neurotoxicity in Alzheimer’s disease. Nature 1996;382:685-9
  • Deane R, Singh I, Sagare AP, et al. A multimodel RAGE-specific inhibitor reduces amyloid b–mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest 2012;122:1377-92
  • Butovsky O, Koronyo-Hamaoui M, Kunis G, et al. Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglial expressing insulin-like growth factor 1. Proc Natl Acad Sci USA 2006;103:11784-9
  • Miron VE, Boyd A, Zhao J-W, et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci 2013;16:1211-14
  • Grathwohl SA, Kalin RE, Bolmont T, et al. Formation and maintenance of Alzheimer’s disease b–amyloid plaques in the absence of microglia. Nat Neurosci 2009;12:1361-4
  • Schenk D, Barbour R, Dunn W, et al. Immunization with amyloid-beta attenuates Alzheimer disease-like pathology in the PDAPP mouse. Nature 1999;400:10016-20
  • Das P, Murphy MP, Younkin LH, et al. Reduced effectiveness of Ab1-42 immunization in APP transgenic mice with significant amyloid deposition. Neurobiol Aging 2001;22:721-7
  • DeMattos RB, Bales KR, Cummins DJ, et al. Peripheral anti-Abeta antibody alters CNS and plasma Abeta clearance and decreases brain Abeta burden in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 2001;98:8850-5
  • Krabbe G, Halle A, Matyash J, et al. Functional impairment of microglia coincides with beta-amyloid deposition in mice with Alzheimer-like pathology. PLoS One 2013;8(4):e60921
  • Nemirovsky A, Shapiro J, Baron R, et al. Ab vaccination fails to enhance amyloid clearance in a mouse model of Alzheimer’s disease with Ab42-driven pathology. J Neuroimmunol 2012;247:95-9
  • Orgogozo JM, Gilman S, Dartigues JF, et al. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 2003;61:46-54
  • Steinberg D. Companies halt first Alzheimer vaccine trial. Scientist 2002;162:2
  • Holmes C, Boche D, Wilkinson D, et al. Long term effects of Ab42 immunization in Alzheimer’s disease: follow-up of a randomized, placebo-controlled phase 1 trial. Lancet 2008;3722:16-23
  • Ostrowitzki S, Deptula D, Thurfjell L, et al. Mechanism of amyloid removal in patients with Alzheimer’s disease treated with gantenerumab. Arch Neurol 2012;69:198-207
  • Nicoll JA, Wilkinson D, Holmes C, et al. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 2003;9:448-52
  • Morkuniene R, Zvirbliene A, Dalgediene I, et al. Antibodies bound to Ab potentiate the neurotoxicity of Ab by activating microglia. J Neurochem 2013;126:604-15
  • Salloway S, Sperling R, Raskind M, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med 2014;370:322-33
  • Doody RS, Thomas RG, Farlow M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 2014;370:311-21
  • La Porte SL, Bollini SS, Lanz TA. Structural basis of C-terminal b-amyloid peptide binding by the antibody ponezumab for the treatment of Alzheimer’s disease. J Mol Biol 2012;421:525-36
  • Mullard A. String of Alzheimer’s failures offset by upcoming prevention trials. Nat Rev Drug Discov 2012;11:657-60
  • Cummings JL, Morstorf T, Zhang K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther 2014;63:7
  • Bateman RJ, Xiong C, Benziger TLS, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012;367:793-804
  • Villemagne VL, Burnham S, Bourgeat P, et al. Amyloid b deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 2013;12:357-67
  • Seppala TT, Nerg O, Koivisto AM, et al. CSF biomarkers for Alzheimer disease correlate with brain atrophy findings. Neurology 2012;781:1568-75
  • Prestia A, Caroll A, van der Flier WM, et al. Prediction of dementia in MCI patients based on core diagnostic markers for Alzheimer disease. Neurology 2013;80:1048-56
  • Buchhave P, Minthon L, Zetterberg H, et al. Cerebrospinal fluid levels of b-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry 2012;69:98-106
  • McKee AC, Cantu RC, Nowinski CJ, et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 2009;682:709-35
  • McKee AC, Stein TD, Nowinski CJ, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain 2013;136:43-64
  • Bermajo-Parejo F, Antequera S, Vargas T, et al. Saliva levels of Abeta1-42 as a potential marker of Alzheimer’s disease. BMC Neurol 2010;10:108-14
  • Shi M, Sui Y-T, Peskrad JR, et al. Salivary tau species are potential markers of Alzheimer disease. J Alzheimers Dis 2011;27:299-305
  • Martin-Mareno AM, Brera B, Spuch C, et al. Prolonged cannabinoid administration prevents neuroinflammation and lowers b-amyloid levels and improves cognitive performance in TgAPP 2576 mice. J Neuroinflammation 2012;9:8
  • Lee YJ, Choi DY, Lee YM, et al. 4-O-Methylhonokiol prevents memory impairment in the Tg2576 transgenic mice model of Alzheimer’s disease via regulation of b-secretase activity. J Alzheimer Dis 2012;29:677-90
  • Biscaro B, Lindvall O, Tesco G, et al. Inhibition of microglial activation protects hippocampal neurogenesis and improves cognitive deficits in a transgenic mouse model for Alzheimer’s disease. Neurodegener Dis 2012;91:87-98
  • Gabbita SP, Srivastava MK, Eslami P, et al. Early intervention with a small molecule inhibitor for tumor necrosis factor− a prevents cognitive deficits in a triple transgenic model of Alzheimer’s disease. J Neuroinflammation 2012;9:99
  • Kurata T, Miyazaki K, Kozuki M, et al. Atorastatin and pitastatin reduce senile plaques and inflammatory responses in a mouse model of Alzheimer’s disease. Neurol Res 2012;34:601-10
  • He P, Cheng X, Staufenbiel M, et al. Long-term treatment of thalidomide ameliorates amyloid-like pathology through inhibition of b-secretase in a mouse model of Alzheimer’s disease. PLoS One 2013;8(2):e55091
  • Lee YW, Kim DH, Jeon SJ, et al. Neuroprotective effects of salvianolic acid B on an Ab 2:5-3:5 peptide induced model of Alzheimer’s disease. Eur J Pharmacol 2013;704:70-7
  • Medeiros R, Kitazawa M, Passos GF, et al. Aspirin-triggered lipoxin A4 stimulates alternative activation of microglia and reduced Alzheimer disease-like pathology in mice. Am J Pathol 2013;182:1780-9
  • Lim GP, Yang F, Chu T, et al. Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice. Neurobiol Aging 2001;22:983-91
  • Sivilia S, Lorenzini L, Giuliani X, et al. Multi-target action of the novel anti-Alzheimer compound CHF:5074; in vivo study of long-term effects in Tg2:576 mice. BMC Neurosci 2013;14:44
  • Fan H, Guo Y, Liang X, et al. Hydrogen sulfide protects against amyloid beta-peptide induced neuronal injury via attenuating inflammatory responses in a rat model. J Biomed Res 2013;272:96-304
  • Meng QH, Lou FL, Hou WX, et al. Acetylpuerarin reduces inflammation and improves memory function in a rat model of Alzheimer’s disease induced by Abeta1-42. Pharmazie 2013;68:904-8
  • Luccarini I, Ed Dami T, Grossi C, et al. Oleuropein aglycone counteracts Ab42 toxicity in the rat brain. Neurosci Lett 2014;558:67-72
  • Kim HG, Moon M, Choi JG, et al. Donepezil inhibits the amyloid-beta oligomer-induced microglial activation in vitro and in vivo. Neurotoxicology 2014;40:23-32
  • Hensley K, Gabbita SP, Venkova K, et al. A derivative of the brain metabolite lanthionine ketimine improves cognition and diminishes pathology in the 3 x Tg-AD mouse model of Alzheimer disease. J Neuropathol Exp Neurol 2013;72:955-69
  • Hu Y, Li C, Shen W. Gastrodin alleviates memory deficits and reduces neuropathology in a mouse model of Alzheimer’s disease. Neuropathology 2014;34(4):370-7
  • Moon M, Choi JG, Kim SY, Oh MS. Bombycis excrementum reduces amyloid-b-oligomer-induced memory impairments, neurodegeneration and neuroinflammation in mice. J Alzheimer Dis 2014;41:599-613
  • Nguyen TV, Shen L, Vander Griend L, et al. Small molecule p7:5NTR ligands reduce pathological phosphorylation and misfolding of tau, inflammatory changes, cholinergic degeneration, and cognitive deficits in AbPPL/S transgenic mice. J Alzheimer Dis 2014
  • Xue D, Zhao M, Wang YJ, et al. A multifunctional peptide rescues memory deficits in Alzheimer’s disease transgenic mice by inhibiting Ab42-induced cytotoxcity and increasing microglial phaocytosis. Neurobiol Dis 2012;46:701-9
  • Lull ME, Levesque S, Surace MJ, Block ML. Chronic apocyanin treatment attenuates beta amyloid plaque size and microglial number in hAPP[751)(SL) mice. PLoS One 2011;6(5):e20153
  • Jia L, Liu J, Song Z, et al. Berberine suppresses amyloid-beta–induced inflammatory response in microglia by inhibiting nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways. J Pharm Pharmacol 2012;64:1510-21
  • Bernardi A, Frozza RL, Meneghetti A, et al. Indomethacin-loaded lipid-core nanocapsules reduce the damage triggered by Ab1-42 in Alzheimer’s disease models. Int J Nanomedicine 2012;7:4927-42
  • Hjorth E, Zhu M, Toro VC, et al. Omega-3 fatty acids enhance phagocytosis of Alzheimer’s disease-related amyloid- b42 by human microglia and decrease inflammatory markers. J Alzhemier Dis 2013;3:697-713
  • Wang CJ, Chen CL, Tsay HJ, et al. Cudrania cochinchinensis attenuates amyloid b protein- mediated microglial activation and promotes glia-related clearance of amyloid B protein. J Biomed Sci 2013;20:55
  • Lee M, McGeer E, Kodela R, et al. NOSH-aspirin (NBS-1120], a novel nitric oxide and hydrogen sulfide releasing hybrid, attenuates neuroinflammation induced by microglial and astrocytic activation: a new candidate for treatment of neurodegenerative disorders. Glia 2013;611:724-34
  • Behensky AA, Yasny IE, Shuster AM, et al. Stimulation of sigma receptors blocks activation of microglia and reduces toxicity caused by amyloid- b25-35. J Pharmacol Exp Ther 2013;347:487-67
  • Qi Y, Zou LB, Wang LH, et al. Xanthoceraside inhibits pro-inflammatory cytokine expression in Ab25-35/IFN−g-stimulated microglia through the TLR2 receptor, MyD88, nuclear factor-kB, and mitogen-activated protein kinase signaling pathways. J Pharmacol Sci 2013;122:305-17
  • Owona BA, Njayou NF, Laufer SA, et al. Entada Africana fraction CH2Cl2/MEOH: 5% inhibits inducible nitric oxide synthase and proinflammatory cytokines gene expression induced by lipopolysaccaharide in microglia. BMC Complement Altern Med 2013;13:254
  • Lee M, Kwon B-M, Suk K, et al. Effects of obovatol on GSH depleted glia-mediated neurotoxicity and oxidative damage. J Neuroimmune Pharmacol 2012;7:173-86
  • Park SY, Lee YH, Seong AR, et al. Selective inhibition of PCAF suppresses microglial-mediated b–amyloid neurotoxicity. Int J Mol Med 2013;32:469-75
  • Guo Y, Shi S, Tong M, et al. The suppressive effects of gx-50 on Ab-induced chemotactic migration of microglia. Int Immunopharmacol 2014;19:283-9

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.