Macrophages in Alzheimer’s disease: the blood-borne identity

Gate, David; Rezai-Zadeh, Kavon; Jodry, Dominique; Rentsendorj, Altan; Town, Terrence

doi:10.1007/s00702-010-0422-7

Cited by 107Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Macrophages in Alzheimer’s disease: the blood-borne identity

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Gate, David, Rezai-Zadeh, Kavon, Jodry, Dominique, Rentsendorj, Altan, Town, Terrence·2010·Journal of Neural Transmission

DOI 10.1007/s00702-010-0422-7PMC PMC2917548

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Abstract

Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder clinically characterized by cognitive decline involving loss of memory, reasoning and linguistic ability. The amyloid cascade hypothesis holds that mismetabolism and aggregation of neurotoxic amyloid-beta (Abeta) peptides, which are deposited as amyloid plaques, are the central etiological events in AD. Recent evidence from AD mouse models suggests that blood-borne mononuclear phagocytes are capable of infiltrating the brain and restricting beta-amyloid plaques, thereby limiting disease progression. These observations raise at least three key questions: (1) what is the cell of origin for macrophages in the AD brain, (2) do blood-borne macrophages impact the pathophysiology of AD and (3) could these enigmatic cells be therapeutically targeted to curb cerebral amyloidosis and thereby slow disease progression? This review begins with a historical perspective of peripheral mononuclear phagocytes in AD, and moves on to critically consider the controversy surrounding their identity as distinct from brain-resident microglia and their potential impact on AD pathology.

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Peripheral macrophages are more efficient phagocytes of Aβ than microglia.
“Furthermore, peripheral macrophages may not just be bystanders in the progression of AD, as it has been shown that they are not only more efficient phagocytes of Aβ than microglia, but they are also capable of traversing the blood-brain barrier during times of injury and disease [17–21].”
From Alzheimer’s disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner (2024) · cites this paper as [17]
Peripheral macrophages are capable of traversing the blood-brain barrier during times of injury and disease.
“Furthermore, peripheral macrophages may not just be bystanders in the progression of AD, as it has been shown that they are not only more efficient phagocytes of Aβ than microglia, but they are also capable of traversing the blood-brain barrier during times of injury and disease [17–21].”
From Alzheimer’s disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner (2024) · cites this paper as [17]

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Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Blood Monocytes Consist of Two Principal Subsets with Distinct Migratory Properties
Geissmann, F., Jung, S., & Littman, D. R. (2003) · Immunity · doi:10.1016/s1074-7613(03)00174-2 · Cited by 3,366 · see citing works
Amyloid deposition as the central event in the aetiology of Alzheimer’s disease
Hardy, J., & Allsop, D. (1991) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(91)90609-v · Cited by 2,538 · see citing works
Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective
Tanzi, R. E., & Bertram, L. (2005) · Cell · doi:10.1016/j.cell.2005.02.008 · Cited by 1,849 · see citing works
Turning Blood into Brain: Cells Bearing Neuronal Antigens Generated in Vivo from Bone Marrow
Mezey, É., Chandross, K. J., Harta, G., Maki, R. A., & McKercher, S. R. (2000) · Science · doi:10.1126/science.290.5497.1779 · Cited by 1,822 · see citing works
From Marrow to Brain: Expression of Neuronal Phenotypes in Adult Mice
Brazelton, T. R., Rossi, F. M. V., Keshet, G. I., & Blau, H. M. (2000) · Science · doi:10.1126/science.290.5497.1775 · Cited by 1,676 · see citing works
Local self-renewal can sustain CNS microglia maintenance and function throughout adult life
Ajami, B., Bennett, J. L., Krieger, C., Tetzlaff, W., & Rossi, F. M. V. (2007) · Nature Neuroscience · doi:10.1038/nn2014 · Cited by 1,643 · see citing works
Long-term effects of Aβ42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial
Holmes, C., Boche, D., Wilkinson, D., Yadegarfar, G., Hopkins, V., Bayer, A., Jones, R. W., Bullock, R., Love, S., Neal, J. W., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61075-2 · Cited by 1,416 · cited 3× · see citing works
“Importantly, CAA severity correlates with degree of dementia in humans (Attems et al. 2005), although there has been much debate about whether CAA is a driving force in the pathobiology of AD. Yet, CAA may represent an important therapeutic target in AD. Recently, Hawkes and McLaurin showed that a perivascular subset…”
Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report
Nicoll, J. A. R., Wilkinson, D., Holmes, C., Steart, P., Markham, H., & Weller, R. O. (2003) · Nature Medicine · doi:10.1038/nm840 · Cited by 1,397 · see citing works
Untitled work
Wyss-Coray (2006) · doi:10.1038/nm1484 · Cited by 1,284 · see citing works
Bone Marrow-Derived Microglia Play a Critical Role in Restricting Senile Plaque Formation in Alzheimer's Disease
Simard, A. R., Soulet, D., Gowing, G., Julien, J.-P., & Rivest, S. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.022 · Cited by 1,265 · see citing works
Subpopulations of Mouse Blood Monocytes Differ in Maturation Stage and Inflammatory Response
Sunderkötter, C., Nikolic, T., Dillon, M. J., van Rooijen, N., Stehling, M., Drevets, D. A., & Leenen, P. J. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.7.4410 · Cited by 1,124 · see citing works
Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
Mildner, A., Schmidt, H., Nitsche, M., Merkler, D., Hanisch, U.-K., Mack, M., Heikenwalder, M., Brück, W., Priller, J., & Prinz, M. (2007) · Nature Neuroscience · doi:10.1038/nn2015 · Cited by 1,089 · see citing works
Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice
Eglitis, M. A., & Mezey, É. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4080 · Cited by 1,015 · see citing works
Amino Acid Homology Between the Encephalitogenic Site of Myelin Basic Protein and Virus: Mechanism for Autoimmunity
Fujinami, R. S., & Oldstone, M. B. A. (1985) · Science · doi:10.1126/science.2414848 · Cited by 947 · see citing works
Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease
El Khoury, J., Toft, M., Hickman, S. E., Means, T. K., Terada, K., Geula, C., & Luster, A. D. (2007) · Nature Medicine · doi:10.1038/nm1555 · Cited by 915 · see citing works
Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain
Alliot, F., Godin, I., & Pessac, B. (1999) · Developmental Brain Research · doi:10.1016/s0165-3806(99)00113-3 · Cited by 884 · see citing works
Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain
Colton, C. A. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9164-4 · Cited by 871 · see citing works
Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis
Greter, M., Heppner, F. L., Lemos, M. P., Odermatt, B. M., Goebels, N., Laufer, T., Noelle, R. J., & Becher, B. (2005) · Nature Medicine · doi:10.1038/nm1197 · Cited by 862 · see citing works
The role of microglia and macrophages in the pathophysiology of the CNS
Stollg, G., & Jander, S. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00083-5 · Cited by 683 · see citing works
Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment
Priller, J., Flügel, A., Wehner, T., Boentert, M., Haas, C. A., Prinz, M., Fernández-Klett, F., Prass, K., Bechmann, I., de Boer, B. A., et al. (2001) · Nature Medicine · doi:10.1038/nm1201-1356 · Cited by 637 · see citing works
Inflammation as a causative factor in the aetiology of Parkinson's disease
Whitton, P. S. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707167 · Cited by 625 · see citing works
Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease: The CERAD experience, part XV
Ellis, R. J., Olichney, J. M., Thal, L. J., Mirra, S. S., Morris, J. C., Beekly, D., & Heyman, A. (1996) · Neurology · doi:10.1212/wnl.46.6.1592 · Cited by 561 · see citing works
Origin of dendritic cells in peripheral lymphoid organs of mice
Liu, K., Waskow, C., Liu, X., Yao, K.-H., Hoh, J. J., & Nussenzweig, M. C. (2007) · Nature Immunology · doi:10.1038/ni1462 · Cited by 473 · see citing works
CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS
Beers, D. R., Henkel-Tigges, J., Zhao, W., Wang, J., & Appel, S. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807419105 · Cited by 468 · see citing works
Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease
King, I. L., Dickendesher, T. L., & Segal, B. M. (2009) · Blood · doi:10.1182/blood-2008-07-168575 · Cited by 444 · see citing works
Sustained hippocampal IL-1β overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology
Shaftel, S. S., Kyrkanides, S., Olschowka, J. A., Miller, J.-N. H., Johnson, R. E., & O’Banion, M. K. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31450 · Cited by 433 · see citing works
Blocking TGF-β–Smad2/3 innate immune signaling mitigates Alzheimer-like pathology
Town, T., Laouar, Y., Pittenger, C., Mori, T., Szekely, C. A., Tan, J., Duman, R. S., & Flavell, R. A. (2008) · Nature Medicine · doi:10.1038/nm1781 · Cited by 422 · see citing works
Self-citation
Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia
Grathwohl, S. A., Kälin, R. E., Bolmont, T., Prokop, S., Winkelmann, G., Kaeser, S. A., Odenthal, J., Radde, R., Eldh, T., Gandy, S., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2432 · Cited by 401 · see citing works
Increased plasma levels of interleukin-1, interleukin-6 and α-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain?
Licastro, F., Pedrini, S., Caputo, L., Annoni, G., Davis, L. J., Ferri, C., Casadei, V. M., & Grimaldi, L. M. E. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00226-x · Cited by 400 · see citing works
Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy
Hawkes, C. A., & McLaurin, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805453106 · Cited by 397 · see citing works
Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1
Butovsky, O., Koronyo-Hamaoui, M., Kunis, G., Ophir, E., Landa, G., Cohen, H., & Schwartz, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604681103 · Cited by 388 · see citing works
T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS
Chiu, I., Chen, A., Zheng, Y., Kosaras, B., Tsiftsoglou, S., Vartanian, T., Brown, R. H., & Carroll, M. (2008) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0804610105 · Cited by 374 · see citing works
Massive gliosis induced by interleukin‐6 suppresses Aβ deposition <i>in vivo:</i> evidence against inflammation as a driving force for amyloid deposition
Chakrabarty, P., Jansen‐West, K., Beccard, A., Ceballos‐Diaz, C., Levites, Y., Verbeeck, C., Zubair, A. C., Dickson, D., Golde, T. E., & Das, P. (2010) · The FASEB Journal · doi:10.1096/fj.09-141754 · Cited by 328 · see citing works
SHIP Represses the Generation of Alternatively Activated Macrophages
Rauh, M. J., Ho, V. W., Pereira, C. C., Sham, A. P., Sly, L. M., Lam, V., Huxham, L. A., Minchinton, A. I., Mui, A., & Krystal, G. (2005) · Immunity · doi:10.1016/j.immuni.2005.09.003 · Cited by 298 · see citing works
Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce ?-amyloid fibrils
Frackowiak, J., Wisniewski, H. M., Wegiel, J., Merz, G. S., Iqbal, K., & Wang, K. C. (1992) · Acta Neuropathologica · doi:10.1007/bf00227813 · Cited by 276 · see citing works
Formation and maintenance of Alzheimer’s disease beta-amyloid plaques in the absence of microglia
Grathwohl, S. A., Kälin, R., Bolmont, T., Prokop, S., Winkelmann, G., Kaeser, S. A., Odenthal, J., Radde, R., Eldh, T., Gandy, S. E., et al. (2010) · e-Neuroforum · doi:10.1515/nf-2010-0107 · Cited by 269 · see citing works
Ultrastructural Studies of the Cells Forming Amyloid Fibers in Classical Plaques
Wisniewski, H. M., Węgiel, J., WANG, K. C., Kujawa, M., & Lach, B. (1989) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100029887 · Cited by 244 · see citing works
Chronic Interleukin-1β Expression in Mouse Brain Leads to Leukocyte Infiltration and Neutrophil-Independent Blood–Brain Barrier Permeability without Overt Neurodegeneration
Shaftel, S. S., Carlson, T. J., Olschowka, J. A., Kyrkanides, S., Matousek, S. B., & O'Banion, M. K. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1418-07.2007 · Cited by 243 · see citing works
Characterization of microglia and macrophages in the central nervous system of rats: Definition of the differential expression of molecules using standard and novel monoclonal antibodies in normal CNS and in four models of parenchymal reaction
Flaris, N. A., Densmore, T. L., Molleston, M. C., & Hickey, W. F. (1993) · Glia · doi:10.1002/glia.440070108 · Cited by 224 · see citing works
Powerful beneficial effects of macrophage colony-stimulating factor on -amyloid deposition and cognitive impairment in Alzheimer's disease
Boissonneault, V., Filali, M., Lessard, M., Relton, J., Wong, G., & Rivest, S. (2008) · Brain · doi:10.1093/brain/awn331 · Cited by 221 · see citing works
Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing
Town, T., Bai, F., Wang, T., Kaplan, A. T., Qian, F., Montgomery, R. R., Anderson, J. F., Flavell, R. A., & Fikrig, E. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.012 · Cited by 217 · see citing works
Self-citation
Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients
Huell, M., Strauss, S., Volk, B., Berger, M., & Bauer, J. (1995) · Acta Neuropathologica · doi:10.1007/bf00571510 · Cited by 214 · see citing works
CNS Infiltration of Peripheral Immune Cells: D-Day for Neurodegenerative Disease?
Rezai-Zadeh, K. P., Gate, D., & Town, T. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9166-2 · Cited by 194 · see citing works
Self-citation
Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy
Attems, J., Jellinger, K. A., & Lintner, F. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-1064-y · Cited by 188 · see citing works
Invasion of Hematopoietic Cells into the Brain of Amyloid Precursor Protein Transgenic Mice
Stalder, A. K., Ermini, F., Bondolfi, L., Krenger, W., Burbach, G. J., Deller, T., Coomaraswamy, J., Staufenbiel, M., Landmann, R. M., & Jucker, M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2545-05.2005 · Cited by 183 · see citing works
T-Cells in Alzheimer's Disease
Town, T., Tan, J., Flavell, R. A., & Mullan, M. (2005) · NeuroMolecular Medicine · doi:10.1385/nmm:7:3:255 · Cited by 183 · see citing works
Self-citation
Selective ablation of bone marrow‐derived dendritic cells increases amyloid plaques in a mouse Alzheimer's disease model
Butovsky, O., Kunis, G., Koronyo‐Hamaoui, M., & Schwartz, M. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05652.x · Cited by 167 · see citing works
Taking Advantage of the Systemic Immune System to Cure Brain Diseases
Yong, V. W., & Rivest, S. (2009) · Neuron · doi:10.1016/j.neuron.2009.09.035 · Cited by 165 · see citing works
The Ly-6Chigh Monocyte Subpopulation Transports Listeria monocytogenes into the Brain during Systemic Infection of Mice
Drevets, D. A., Dillon, M. J., Schawang, J. S., van Rooijen, N., Ehrchen, J. M., Sunderkötter, C. H., & Leenen, P. J. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.7.4418 · Cited by 160 · see citing works
Hematopoietic cells maintain hematopoietic fates upon entering the brain
Massengale, M., Wagers, A. J., Vogel, H. S., & Weissman, I. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050030 · Cited by 159 · see citing works
Ultrastructural Location of Major Histocompatibility Complex (MHC) Class II Positive Perivascular Cells in Histologically Normal Human Brain
Graeber, M. B., Streit, W. J., Büringer, D., Sparks, D. L., & Kreutzberg, G. W. (1992) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199205000-00009 · Cited by 149 · see citing works
Resident and Infiltrating Central Nervous System APCs Regulate the Emergence and Resolution of Experimental Autoimmune Encephalomyelitis
Juedes, A. E., & Ruddle, N. H. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.8.5168 · Cited by 145 · see citing works
Butovsky, O. et al. Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proc. Natl Acad. Sci. USA 103, 11784-11789
Butovsky, O., Koronyo‐Hamaoui, M., Kunis, G., Ophir, E., Landa, G., Cohen, H., & Schwartz, M. (2006) · Cited by 144 · see citing works
Immune processes in the pathogenesis of Parkinson's disease - a potential role for microglia and nitric oxide.
Członkowska, A., Kurkowska‐Jastrzębska, I., Członkowski, A., Peter, D., & Stefano, G. B. (2002) · PubMed · Cited by 123 · see citing works
CCL2 Accelerates Microglia-Mediated Aβ Oligomer Formation and Progression of Neurocognitive Dysfunction
Kiyota, T., Yamamoto, M., Xiong, H., Lambert, M. P., Klein, W. L., Gendelman, H. E., Ransohoff, R. M., & Ikezu, T. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006197 · Cited by 114 · see citing works
Phagocytosis of ?/A4 amyloid fibrils of the neuritic neocortical plaques
Wisniewski, H. M., Barcikowska, M., & Kida, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00310142 · Cited by 109 · see citing works
Mature monocytic cells enter tissues and engraft
Kennedy, D. W., & Abkowitz, J. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14944 · Cited by 109 · see citing works
Minute numbers of contaminant CD8+ T cells or CD11b+CD11c+ NK cells are the source of IFN-γ in IL-12/IL-18-stimulated mouse macrophage populations
Schleicher, U., Hesse, A., & Bogdan, C. (2004) · Blood · doi:10.1182/blood-2004-05-1749 · Cited by 90 · see citing works
Neuromodulatory Activities of CD4+CD25+ Regulatory T Cells in a Murine Model of HIV-1-Associated Neurodegeneration
Liu, J., Gong, N., Huang, X., Reynolds, A. D., Mosley, R. L., & Gendelman, H. E. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803330 · Cited by 89 · see citing works
Systemic Immune Deviation in the Brain That Does Not Depend on the Integrity of the Blood-Brain Barrier
Wenkel, H., Streilein, J. W., & Young, M. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.10.5125 · Cited by 79 · see citing works
Brain CD8+ and cytotoxic T lymphocytes are associated with, and may be specific for, human immunodeficiency virus type 1 encephalitis in patients with acquired immunodeficiency syndrome
Petito, C. K., Torres-Muñoz, J., Zielger, F., & McCarthy, M. (2006) · Journal of NeuroVirology · doi:10.1080/13550280600879204 · Cited by 51 · see citing works
Cerebral amyloid angiopathy in Lewy body disease
Jellinger, K. A., & Attems, J. (2008) · Journal of Neural Transmission · doi:10.1007/s00702-007-0856-8 · Cited by 50 · see citing works
Alternative Aβ Immunotherapy Approaches for Alzheimers Disease
Town, T. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709787847306 · Cited by 42 · see citing works
Self-citation
Microglia in Alzheimer's Disease and Transgenic Models
Dickson, D. W. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65416-8 · Cited by 39 · see citing works
Can peripheral leukocytes be used as Alzheimer’s disease biomarkers?
Rezai-Zadeh, K. P., Gate, D., Szekely, C. A., & Town, T. (2009) · Expert Review of Neurotherapeutics · doi:10.1586/ern.09.118 · Cited by 37 · see citing works
Self-citation
Separate precursor cells for macrophages and microglia in mouse brain: immunophenotypic and immunoregulatory properties of the progeny
Walker, W. S. G. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00237-9 · Cited by 30 · see citing works
Cerebral and Peripheral Amyloid Phagocytes— an Old Liaison with a New Twist
Jucker, M., & Heppner, F. L. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.014 · Cited by 26 · see citing works
[Microglia: origin and development].
Pessac, B., Godin, I., & Alliot, F. (2001) · PubMed · Cited by 23 · see citing works

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Microglia development follows a stepwise program to regulate brain homeostasis
Matcovitch-Natan, O., Winter, D. R., Giladi, A., Vargas Aguilar, S., Spinrad, A., Sarrazin, S., Ben-Yehuda, H., David, E., Zelada González, F., Perrin, P., et al. (2016) · Science · doi:10.1126/science.aad8670 · Cited by 1,180 · see citing works
Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases
Yuan, J., Amin, P., & Ofengeim, D. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0093-1 · Cited by 967 · see citing works
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Jay, T. R., Hirsch, A. M., Broihier, M. L., Miller, C. M., Neilson, L. E., Ransohoff, R. M., Lamb, B. T., & Landreth, G. E. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2110-16.2016 · Cited by 457 · see citing works
Inflammatory process in Alzheimer's Disease
Meraz-Ríos, M. A., Toral-Rios, D., Franco-Bocanegra, D., Villeda-Hernández, J., & Campos-Peña, V. (2013) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00059 · Cited by 427 · see citing works
PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease
Baruch, K., Deczkowska, A., Rosenzweig, N., Tsitsou-Kampeli, A., Sharif, A. M., Matcovitch-Natan, O., Kertser, A., David, E., Amit, I., & Schwartz, M. (2016) · Nature Medicine · doi:10.1038/nm.4022 · Cited by 425 · see citing works
Distinct and Non-Redundant Roles of Microglia and Myeloid Subsets in Mouse Models of Alzheimer's Disease
Mildner, A., Schlevogt, B., Kierdorf, K., Böttcher, C., Erny, D., Kummer, M. P., Quinn, M., Brück, W., Bechmann, I., Heneka, M. T., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.6209-10.2011 · Cited by 351 · see citing works
CD8+ T-cells infiltrate Alzheimer’s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice
Unger, M. S., Li, E., Scharnagl, L., Poupardin, R., Altendorfer, B., Mrowetz, H., Hutter-Paier, B., Weiger, T. M., Heneka, M. T., Attems, J., et al. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.05.070 · Cited by 248 · see citing works
Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer's disease
Losurdo, M., Pedrazzoli, M., D’Agostino, C., Elia, C., Massenzio, F., Lonati, E., Mauri, M., Rizzi, L., Molteni, L., Bresciani, E., et al. (2020) · Stem Cells Translational Medicine · doi:10.1002/sctm.19-0327 · Cited by 265 · see citing works
Sex, glia, and development: Interactions in health and disease
Schwarz, J. M., & Bilbo, S. D. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.02.018 · Cited by 247 · see citing works
PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model
Rosenzweig, N., Dvir-Szternfeld, R., Tsitsou-Kampeli, A., Keren‐Shaul, H., Ben-Yehuda, H., Weill-Raynal, P., Cahalon, L., Kertser, A., Baruch, K., Amit, I., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08352-5 · Cited by 224 · see citing works
Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease
Gamba, P., Testa, G., Gargiulo, S., Staurenghi, E., Poli, G., & Leonarduzzi, G. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00119 · Cited by 202 · see citing works
Peripheral and central effects of repeated social defeat stress: monocyte trafficking, microglial activation, and anxiety
Reader, B. F., Jarrett, B. L., McKim, D. B., Wohleb, E. S., Godbout, J. P., & Sheridan, J. F. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.01.001 · Cited by 179 · see citing works
“, multiple sclerosis, traumatic injury, stroke, Alzheimer’s disease, or infection (Hafler et al., 2005; Gate et al., 2010; Donnelly et al., 2011; Hawthorne and Popovich, 2011; McGavern and Kang, 2011; de Vries et al., 2012).”
Background
Migration of neutrophils targeting amyloid plaques in Alzheimer's disease mouse model
Baik, S. H., Cha, M.-Y., Hyun, Y.-M., Cho, H., Hamza, B., Kim, D. K., Han, S.-H., Choi, H., Kim, K. H., Moon, M., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.01.003 · Cited by 181 · see citing works
Mathematical model on Alzheimer’s disease
Hao, W., & Friedman, A. (2016) · BMC Systems Biology · doi:10.1186/s12918-016-0348-2 · Cited by 153 · see citing works
Macrophage Targeted Theranostics as Personalized Nanomedicine Strategies for Inflammatory Diseases
Patel, S. K., & Janjic, J. M. (2014) · Theranostics · doi:10.7150/thno.9476 · Cited by 153 · see citing works
Atherosclerosis and Alzheimer - diseases with a common cause? Inflammation, oxysterols, vasculature
Lathe, R., Tsitrina, A. A., & Kotelevtsev, Y. V. (2014) · BMC Geriatrics · doi:10.1186/1471-2318-14-36 · Cited by 136 · see citing works
Ethnopharmacological Approaches for Dementia Therapy and Significance of Natural Products and Herbal Drugs
Tewari, D., Stankiewicz, A. M., Mocan, A., Sah, A. N., Tzvetkov, N. T., Huminiecki, Ł., Horbańczuk, J. O., & Atanasov, A. G. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00003 · Cited by 136 · see citing works
Phenotypic profile of alternative activation marker CD163 is different in Alzheimer’s and Parkinson’s disease
Pey, P., Pearce, R. K., Kalaitzakis, M. E., Griffin, W. S. T., & Gentleman, S. M. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-21 · Cited by 128 · see citing works
Systemic immune system alterations in early stages of Alzheimer's disease
Zhang, R., Miller, R. G., Madison, C. A., Jin, X., Honrada, R., Harris, W., Katz, J., Forshew, D. A., & McGrath, M. S. (2013) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2013.01.002 · Cited by 121 · see citing works
Microglia prevent peripheral immune cell invasion and promote an anti-inflammatory environment in the brain of APP-PS1 transgenic mice
Unger, M. S., Schernthaner, P., Marschallinger, J., Mrowetz, H., & Aigner, L. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1304-4 · Cited by 113 · see citing works
Neuroprotective Effect of TREM-2 in Aging and Alzheimer’s Disease Model
Raha, A. A., Henderson, J. W., Stott, S., Vuono, R., Foscarin, S., Friedland, R. P., Zaman, S. H., & Raha‐Chowdhury, R. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160663 · Cited by 109 · see citing works
19F magnetic resonance imaging of endogenous macrophages in inflammation
Temme, S., Bönner, F., Schrader, J., & Flögel, U. (2012) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1163 · Cited by 111 · see citing works
Maternal immune activation leads to activated inflammatory macrophages in offspring
Onore, C. E., Schwartzer, J. J., Careaga, M., Berman, R. F., & Ashwood, P. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.02.007 · Cited by 106 · see citing works
Brain injury, neuroinflammation and Alzheimer's disease
Breunig, J. J., Guillot‐Sestier, M., & Town, T. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00026 · Cited by 104 · see citing works
Self-citation
Innate Immunity Fights Alzheimer's Disease
Guillot‐Sestier, M., Doty, K. R., & Town, T. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.008 · Cited by 100 · see citing works
Self-citation
Unilateral Focused Ultrasound-Induced Blood-Brain Barrier Opening Reduces Phosphorylated Tau from The rTg4510 Mouse Model
Karakatsani, M. E., Kugelman, T., Ji, R., Murillo, M. F., Wang, S., Niimi, Y., Small, S. A., Duff, K., & Konofagou, E. E. (2019) · Theranostics · doi:10.7150/thno.28717 · Cited by 98 · see citing works
Microglia in Alzheimer's Disease: It's All About Context
Weitz, T. M., & Town, T. (2012) · International Journal of Alzheimer's Disease · doi:10.1155/2012/314185 · Cited by 95 · see citing works
Self-citation
Microglial morphology in Alzheimer’s disease and after Aβ immunotherapy
Franco-Bocanegra, D., Gourari, Y., McAuley, C., Chatelet, D. S., Johnston, D. A., Nicoll, J. A. R., & Boche, D. (2021) · Scientific Reports · doi:10.1038/s41598-021-95535-0 · Cited by 85 · see citing works
P2 Receptors for Extracellular Nucleotides in the Central Nervous System: Role of P2X7 and P2Y2 Receptor Interactions in Neuroinflammation
Weisman, G. A., Camden, J. M., Peterson, T. S., Ajit, D., Woods, L. T., & Erb, L. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8263-z · Cited by 85 · see citing works
Migration of blood cells to β-amyloid plaques in Alzheimer's disease
Hohsfield, L. A., & Humpel, C. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.03.002 · Cited by 79 · see citing works
Towards Understanding the Roles of Heparan Sulfate Proteoglycans in Alzheimer’s Disease
Zhang, G.-L., Zhang, X., Wang, X., & Li, J. (2014) · BioMed Research International · doi:10.1155/2014/516028 · Cited by 76 · see citing works
Innate Immunity in Alzheimer’s Disease: A Complex Affair
Guillot‐Sestier, M., & Town, T. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527311312050008 · Cited by 71 · see citing works
Self-citation
Linking cardiometabolic disorders to sporadic Alzheimer’s disease: a perspective on potential mechanisms and mediators
Bhat, N. R. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06978.x · Cited by 70 · see citing works
Neutrophil recruitment and leukocyte response following focused ultrasound and microbubble mediated blood-brain barrier treatments
Poon, C., Pellow, C., & Hynynen, K. (2020) · Theranostics · doi:10.7150/thno.52710 · Cited by 68 · see citing works
Trafficking of immune cells across the blood-brain barrier is modulated by neurofibrillary pathology in tauopathies
Majerová, P., Michalicová, A., Cente, M., Hanes, J., Vegh, J., Kittel, Á., Kosikova, N., Cigánková, V., Mihaljević, S., Jadhav, S., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0217216 · Cited by 67 · see citing works
Microglia and astrocyte activation is region‐dependent in the α‐synuclein mouse model of Parkinson's disease
Basurco, L., Abellanas, M. A., Ayerra, L., Conde, E., Vinueza‐Gavilanes, R., Luquin, E., Vales, Á., Vilas, A., Martín‐Úriz, P. S., Tamayo, I., et al. (2022) · Glia · doi:10.1002/glia.24295 · Cited by 64 · see citing works
Heparanase overexpression impairs inflammatory response and macrophage-mediated clearance of amyloid-β in murine brain
Zhang, X., Wang, B., O'Callaghan, P. W., Hjertström, E., Jia, J., Gong, F., Zcharia, E., Nilsson, L. N. G., Lannfelt, L., Vlodavsky, I., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0997-1 · Cited by 65 · see citing works
How to Get from Here to There: Macrophage Recruitment in Alzheimers Disease
Rezai-Zadeh, K. P., Gate, D., Gowing, G., & Town, T. (2011) · Current Alzheimer Research · doi:10.2174/156720511795256017 · Cited by 64 · see citing works
Self-citation
Infiltrating T lymphocytes reduce myeloid phagocytosis activity in synucleinopathy model
Sommer, A., Fadler, T., Dorfmeister, E., Hoffmann, A.-C., Xiang, W., Winner, B., & Prots, I. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0632-5 · Cited by 62 · see citing works
Genetics of Late‐Onset Alzheimer′s Disease: Update from the Alzgene Database and Analysis of Shared Pathways
Olgiati, P., Politis, A. M., Papadimitriou, G. N., Ronchi, D. D., & Serretti, A. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/832379 · Cited by 57 · see citing works
The role of glial cells in Alzheimer disease: potential therapeutic implications
Cabezas, I. L., Batista, A. H., & Rol, G. P. (2014) · Neurología (English Edition) · doi:10.1016/j.nrleng.2012.10.009 · Cited by 57 · see citing works
Myeloid differentiation factor 88-deficient bone marrow cells improve Alzheimer’s disease-related symptoms and pathology
Hao, W., Liu, Y., Liu, S., Walter, S., Grimm, M. O. W., Kiliaan, A. J., Penke, B., Hartmann, T., Rübe, C. E., Menger, M. D., et al. (2010) · Brain · doi:10.1093/brain/awq325 · Cited by 53 · see citing works
Role of Macrophage Dopamine Receptors in Mediating Cytokine Production: Implications for Neuroinflammation in the Context of HIV-Associated Neurocognitive Disorders
Nolan, R. A., Muir, R., Runner, K., Haddad, E. K., & Gaskill, P. J. (2018) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-018-9825-2 · Cited by 54 · see citing works
Systems biology of neurodegenerative diseases
Wood, L. B., Winslow, A. R., & Strasser, S. D. (2015) · Integrative Biology · doi:10.1039/c5ib00031a · Cited by 54 · see citing works
Papel de la glía en la enfermedad de Alzheimer. Futuras implicaciones terapéuticas
Cabezas, I. L., Batista, A. H., & Rol, G. P. (2012) · Neurología · doi:10.1016/j.nrl.2012.10.006 · Cited by 50 · see citing works
Neuroprotective roles of the P2Y2 receptor
Weisman, G. A., Ajit, D., Garrad, R. C., Peterson, T. S., Woods, L. T., Thebeau, C. N., Camden, J. M., & Erb, L. (2012) · Purinergic Signalling · doi:10.1007/s11302-012-9307-6 · Cited by 50 · see citing works
Modulation of SPARC/Hevin Proteins in Alzheimer’s Disease Brain Injury
Strunz, M., Jarrell, J. T., Cohen, D. S., Rosin, E. R., Vanderburg, C. R., & Huang, X. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181032 · Cited by 43 · see citing works
Epitope analysis following active immunization with tau proteins reveals immunogens implicated in tau pathogenesis
Selenica, M.-L. B., Davtyan, H., Housley, S. B., Blair, L. J., Gillies, A., Nordhues, B. A., Zhang, B., Liu, J., Gestwicki, J. E., Lee, D. C., et al. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0152-0 · Cited by 40 · see citing works
Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease
Gu, X., Lai, D., Liu, S., Chen, K., Zhang, P., Chen, B., Huang, G., Cheng, X., & Lu, C. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.949083 · Cited by 40 · see citing works
Current Therapeutic Targets for Alzheimer's Disease
Chaudhary, A., Maurya, P. K., Yadav, B. S., Singh, S., & Mani, A. (2018) · Journal of Biomedicine · doi:10.7150/jbm.26783 · Cited by 38 · see citing works
The effects and potential of microglial polarization and crosstalk with other cells of the central nervous system in the treatment of Alzheimer’s disease
Ma, C., Wu, Y., Song, L., Yin, L., Yin, J.-J., Wang, Q., Yu, J., & Xiao, B. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.355747 · Cited by 37 · see citing works
Ergothioneine, a dietary antioxidant improves amyloid beta clearance in the neuroretina of a mouse model of Alzheimer’s disease
Wijesinghe, P., Whitmore, C. A., Campbell, M., Li, C. H., Tsuyuki, M., To, E. C., Haynes, J. R., Pham, W. N., & Matsubara, J. A. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1107436 · Cited by 36 · see citing works
Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease
Lathe, R., Schultek, N. M., Balin, B. J., Ehrlich, G. D., Alberi, L. A., Perry, G. L., Breitschwerdt, E. B., Corry, D. B., Doty, R. L., Rissman, R. A., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13076 · Cited by 37 · see citing works
Programmed ageing: decline of stem cell renewal, immunosenescence, and Alzheimer's disease
Lathe, R., & Clair, D. S. (2023) · Biological Reviews of The Cambridge Philosophical Society · doi:10.1111/brv.12959 · Cited by 28 · see citing works
Identification of diagnostic signatures associated with immune infiltration in Alzheimer’s disease by integrating bioinformatic analysis and machine-learning strategies
Tian, Y., Lu, Y., Cao, Y., Dang, C., Wang, N., Tian, K., Luo, Q., Guo, E., Luo, S., Wang, L., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.919614 · Cited by 32 · see citing works
The age-related neuroinflammatory environment promotes macrophage activation, which negatively impacts synaptic function
Costello, D. A., Keenan, K., McManus, R. M., Falvey, A., & Lynch, M. A. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.001 · Cited by 32 · see citing works
Innate immunity in Alzheimer’s disease: the relevance of animal models?
Franco-Bocanegra, D., Nicoll, J. A. R., & Boche, D. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1729-4 · Cited by 31 · see citing works
HIV-1 Reduces Aβ-Degrading Enzymatic Activities in Primary Human Mononuclear Phagocytes
Lan, X., Xu, J., Kiyota, T., Peng, H., Zheng, J., & Ikezu, T. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100211 · Cited by 29 · see citing works
Identification of Immune Cells and Key Genes associated with Alzheimer's Disease
Liu, C., Zhang, X., Chai, H., Xu, S., Liu, Q., Luo, Y., & Li, S. (2021) · International Journal of Medical Sciences · doi:10.7150/ijms.66422 · Cited by 28 · see citing works
C5aR agonist enhances phagocytosis of fibrillar and non-fibrillar Aβ amyloid and preserves memory in a mouse model of familial Alzheimer’s disease
Panayiotou, E., Fella, E., Andreou, S., Papacharalambous, R., Gerasimou, P., Costeas, P., Angeli, S., Kousiappa, I., Papacostas, S., & Kyriakides, T. (2019) · PLoS ONE · doi:10.1371/journal.pone.0225417 · Cited by 26 · see citing works
Quantitative whole-cell MALDI-TOF MS fingerprints distinguishes human monocyte sub-populations activated by distinct microbial ligands
Portevin, D., Pflüger, V., Otieno, P., Brunisholz, R., Vogel, G., & Daubenberger, C. (2015) · BMC Biotechnology · doi:10.1186/s12896-015-0140-1 · Cited by 26 · see citing works
Let’s make microglia great again in neurodegenerative disorders
Guillot‐Sestier, M., & Town, T. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1792-x · Cited by 26 · see citing works
Self-citation
Inhibition of Smad3 in macrophages promotes Aβ efflux from the brain and thereby ameliorates Alzheimer's pathology
Xu, L., Pan, C., Wu, X., Song, J., Meng, P., Li, L., Wang, L., Zhang, Z., & Zhang, Z.-Y. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.03.013 · Cited by 25 · see citing works
The Immune System and the Developing Brain
Schwarz, J. M., & Bilbo, S. D. (2011) · Colloquium Series on The Developing Brain · doi:10.4199/c00045ed1v01y201110dbr004 · Cited by 24 · see citing works
Uncovering mechanisms of brain inflammation in Alzheimer's disease with APOE4: Application of single cell‐type lipidomics
Asante, I., Louie, S., & Yassine, H. N. (2022) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14907 · Cited by 22 · see citing works
Vaccines and Dementia: Part II. Efficacy of BCG and Other Vaccines Against Dementia
Greenblatt, C. L., & Lathe, R. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231323 · Cited by 21 · see citing works
Intravenous Infusion of Monocytes Isolated from 2-Week-Old Mice Enhances Clearance of Beta-Amyloid Plaques in an Alzheimer Mouse Model
Hohsfield, L. A., & Humpel, C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121930 · Cited by 21 · see citing works
Alzheimer’s disease and age-related macular degeneration: Shared and distinct immune mechanisms
Butovsky, O., & Rosenzweig, N. (2025) · Immunity · doi:10.1016/j.immuni.2025.04.013 · Cited by 22 · see citing works
Serum DBI and biomarkers of neuroinflammation in Alzheimer’s disease and delirium
Conti, E., Andreoni, S., Tomaselli, D., Storti, B., Brovelli, F., Acampora, R., Re, F. D., Appollonio, I. M., Ferrarese, C., & Tremolizzo, L. (2020) · Neurological Sciences · doi:10.1007/s10072-020-04608-x · Cited by 19 · see citing works
Inflammation/bioenergetics-associated neurodegenerative pathologies and concomitant diseases: a role of mitochondria targeted catalase and xanthophylls
Filippov, M. A., Tatarnikova, O. G., Pozdnyakova, N. V., & Vorobyov, V. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.290878 · Cited by 20 · see citing works
Transport of cargo from periphery to brain by circulating monocytes
Cintron, A. F., Dalal, N. V., Dooyema, J. M., Betarbet, R. S., & Walker, L. C. (2015) · Brain Research · doi:10.1016/j.brainres.2015.06.047 · Cited by 19 · see citing works
Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer's Disease
Jay, T. R., Hirsch, A. M., Broihier, M. L., Miller, C. M., Neilson, L. E., Ransohoff, R. M., Lamb, B. T., & Landreth, G. E. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2110-16.2017 · Cited by 18 · see citing works
Identification of Biomarkers Related to M2 Macrophage Infiltration in Alzheimer’s Disease
Lin, C., Xu, C., Zhou, Y., Chen, A., & Jin, B. (2022) · Cells · doi:10.3390/cells11152365 · Cited by 19 · see citing works
Neuroinflammation and Alteration of the Blood-Brain Barrier in Alzheimer´s Disease
Soto-Rojas, L. O., de la Cruz‐López, F., Ontiveros‐Torres, M. Á., Viramontes‐Pintos, A., Cárdenas‐Aguayo, M. D. C., Meraz‐Ríos, M. A., Salinas‐Lara, C., Florán, B., & Luna‐Muñoz, J. (2015) · InTech eBooks · doi:10.5772/60024 · Cited by 18 · see citing works
The inextricable axis of targeted diagnostic imaging and therapy: An immunological natural history approach
Cope, F. O., Abbruzzese, B. C., Sanders, J., Metz, W., Sturms, K., Ralph, D. A., Blue, M., Zhang, J., Bracci, P. M., Bshara, W., et al. (2015) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2015.11.007 · Cited by 17 · see citing works
Amyloid Cascade into Clarity
Weitz, T. M., & Town, T. (2016) · Immunity · doi:10.1016/j.immuni.2016.10.006 · Cited by 17 · see citing works
Self-citation
Donepezil modulates the endogenous immune response: implications for Alzheimer's disease
Conti, E., Tremolizzo, L., Santarone, M. E., Tironi, M., Radice, I., Zoia, C., Aliprandi, A., Salmaggi, A., Dominici, R., Casati, M., et al. (2016) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2538 · Cited by 17 · see citing works
Emerging advances in nano-biomaterial assisted amyloid beta chimeric antigen receptor macrophages (CAR-M) therapy: reducing plaque burden in Alzheimer’s disease
Kushwaha, N., Panjwani, D., Patel, S., Ahlawat, P., Yadav, M. R., & Patel, A. (2024) · Journal of drug targeting · doi:10.1080/1061186x.2024.2417012 · Cited by 16 · see citing works
The role of monocytes and macrophages in the progression of Alzheimer’s disease
Nie, W., Yue, Y., & Hu, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1590909 · Cited by 15 · see citing works
The generation of NGF-secreting primary rat monocytes: A comparison of different transfer methods
Hohsfield, L. A., Geley, S., Reindl, M., & Humpel, C. (2013) · Journal of Immunological Methods · doi:10.1016/j.jim.2013.02.016 · Cited by 14 · see citing works
Microglial cGAS deletion protects against amyloid-β induced Alzheimer’s disease pathogenesisPreprint
He, S., Li, X., Mittra, N., Bhattacharjee, A., Wang, H., Zhao, S., Liu, F., & Han, X. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.07.552300 · Cited by 12 · see citing works
Nigrostriatal degeneration determines dynamics of glial inflammatory and phagocytic activity
Ayerra, L., Abellanas, M. A., Basurco, L., Tamayo, I., Conde, E., Tavira, A., Trigo, A., Vidaurre, C., Vilas‐Zornoza, A., Martín‐Úriz, P. S., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03091-x · Cited by 11 · see citing works
Neutrophil–Lymphocytes Ratio as Potential Early Marker for Alzheimer’s Disease
Cervellati, C., Pedrini, D., Pirro, P., Guindani, P., Renzini, C., Brombo, G., & Zuliani, G. (2024) · Mediators of Inflammation · doi:10.1155/2024/6640130 · Cited by 11 · see citing works
Dysfunctional macrophages in Alzheimer Disease: another piece of the “macroph-aging” puzzle?
Costarelli, L., Malavolta, M., Giacconi, R., & Provinciali, M. (2017) · Aging · doi:10.18632/aging.101276 · Cited by 10 · see citing works
Alzheimer’s disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner
Staley, H. A., Jernigan, J. E., Bolen, M. L., Titus, A. M., Neighbarger, N., Cole, C., Menees, K. B., Wallings, R. L., & Tansey, M. G. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03271-9 · Cited by 9 · see citing works
“Furthermore, peripheral macrophages may not just be bystanders in the progression of AD, as it has been shown that they are not only more efficient phagocytes of Aβ than microglia, but they are also capable of traversing the blood-brain barrier during times of injury and disease [17–21].”
Background
Identification of diagnostic molecules and potential traditional Chinese medicine components for Alzheimer’s disease by single cell RNA sequencing combined with a systematic framework for network pharmacology
Wang, T., Zhang, X., Liu, W., Ning, F., Hu, X., Qin, L., Cui, M., Yang, J., Lv, S., & Wang, Q. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2023.1335512 · Cited by 9 · see citing works
Effects of low-intensity ultrasound opening the blood-brain barrier on Alzheimer's disease—a mini review
Zhou, M., Fu, X., Ma, B., Chen, Z., Cheng, Y., Liu, L., Kan, S., Zhao, X., Feng, S., Jiang, Z., et al. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1274642 · Cited by 9 · see citing works
Exercise Training-Increased FBXO32 and FOXO1 in a Gender-Dependent Manner in Mild Cognitively Impaired African Americans: GEMS-1 Study
Bedada, F., Ntekim, O. E., Nwulia, E., Fungwe, T., Nadarajah, S., & Obisesan, T. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.641758 · Cited by 8 · see citing works
Migration Inhibition Factor Secreted by Peripheral Blood Memory B Cells Binding to CD74-CD44 Receptor Complex Drives Macrophage Behavior in Alzheimer’s Disease
Liu, B., Luo, W., Huang, L., Wei, C., Huang, X., Liu, J., Tao, R., Mo, Y., & Li, X. (2024) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/15333175241238577 · Cited by 8 · see citing works
Aspectos celulares e fisiológicos da Barreira Hematoencefálica
Vieira, G. D. D., & de Sousa, C. M. (2013) · Journal of Health & Biological Sciences · doi:10.12662/2317-3076jhbs.v1i4.38.p166.2013 · Cited by 7 · see citing works
Generative artificial intelligence, integrative bioinformatics, and single-cell analysis reveal Alzheimer’s genetic and immune landscape
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BASIC NEUROSCIENCES, GENETICS AND IMMUNOLOGY- REVIEW ARTICLE Macrophages in Alzheimer’s disease: the blood-borne identity
Gate, D., Rezai-Zadeh, K. P., Jodry, D., Rentsendorj, A., Town, T., Gate, D., Rezai-zadeh, K., Jodry, D., Rentsendorj, A., Town, T., et al. (2013)
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Authors: Gate, D., Rezai-Zadeh, K., Jodry, D., Rentsendorj, A., & Town, T.
Affiliations: Cedars-Sinai Medical Center (US)
Corresponding author: Town, Terrence
ORCID: Gate, David
Rezai-Zadeh, Kavon
Rentsendorj, Altan
Venue: Journal of Neural Transmission
Publisher: Springer Science and Business Media LLC
Published: 2010-06-02
Volume: 117
Issue: 8
Pages: 961-970
ISSN: 0300-9564 (ISSN-L)
1435-1463
DOI: 10.1007/s00702-010-0422-7
PMC: PMC2917548
OpenAlex: W2058092975
Cited by: 107
References: 69
Citations by year: 2026: 2 · 2025: 3 · 2024: 12 · 2023: 5 · 2022: 8 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 10 · 2015: 12 · 2014: 8 · 2013: 6 · 2012: 7
FWCI: 0.56
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: Journal of Neural Transmission (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion, other-oa)
eScholarship (California Digital Library) (submittedVersion)
Funders: Case Western Reserve University
University of South Florida
National Institutes of Health
National Institute on Aging (R00AG029726)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: Alzheimer's disease, macrophages, microglia, amyloid-beta, amyloid plaques, cerebral amyloidosis, cell of origin, therapeutic targeting, neuroinflammation
MeSH terms: Alzheimer Disease, Animals, Blood-Brain Barrier, Brain, Humans, Macrophages, Models, Biological

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Macrophages in Alzheimer’s disease: the blood-borne identity

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