Cited by 216Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

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Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease

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Farfara, D., Lifshitz, V., Frenkel, D.·2008·Journal of Cellular and Molecular Medicine

DOI 10.1111/j.1582-4934.2008.00314.xPMC PMC4401126

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Abstract

• Introduction • Innate immune response in the AD brain - Microglia - Astrocyte • Glial cells mediate the peripheral immune response in AD - Glial cell interaction with endothelial cells - Glial cell interaction with T cells • Glial cell activation as a therapeutic target in AD • Conclusion Alzheimer's disease (AD) affects more than 18 million people worldwide and is characterized by progressive memory deficits, cognitive impairment and personality changes. The main cause of AD is generally attributed to the increased production and accumulation of amyloid-β (Aβ), in association with neurofibrillary tangle (NFT) formation. Increased levels of pro-inflammatory factors such as cytokines and chemokines, and the activation of the complement cascade occurs in the brains of AD patients and contributes to the local inflammatory response triggered by senile plaque. The existence of an inflammatory component in AD is now well known on the basis of epidemiological findings showing a reduced prevalence of the disease upon long-term medication with anti-inflammatory drugs, and evidence from studies of clinical materials that shows an accumulation of activated glial cells, particularly microglia and astrocytes, in the same areas as amyloid plaques. Glial cells maintain brain plasticity and protect the brain for functional recovery from injuries. Dysfunction of glial cells may promote neurodegeneration and, eventually, the retraction of neuronal synapses, which leads to cognitive deficits. The focus of this review is on glial cells and their diversity properties in AD.

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Interleukin-1, neuroinflammation, and Alzheimer's disease
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“Pro-inflammatory cytokines, such as interleukin1 (IL-1 / [36, 37], tumour necrosis factor- (TNF- ) [38] and IL-6 [39], may play an important role in AD pathology and lead to an increased production of inducible nitric oxide synthase (iNOS), neuronal stress and further neuronal dysfunction and death [40].”
Background
Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease
Fonseca, M. I., Zhou, J., Botto, M., & Tenner, A. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0901-04.2004 · Cited by 345 · cited 1×
“Furthermore, the absence of C1q leads to less neuropathology in transgenic mouse models of AD [28].”
Background
Complement components of the innate immune system in health and disease in the CNS
Gasque, P., Dean, Y. D., McGreal, E. P., VanBeek, J., & Morgan, B. P. (2000) · Immunopharmacology · doi:10.1016/s0162-3109(00)80302-1 · Cited by 343 · cited 3×
“The complement system provides an innate immune response against pathogenic features and contributes to the local inflammatory response triggered by A deposition and NFT in AD [17, 22].”
Background
Microglial Activation and β-Amyloid Deposit Reduction Caused by a Nitric Oxide-Releasing Nonsteroidal Anti-Inflammatory Drug in Amyloid Precursor Protein Plus Presenilin-1 Transgenic Mice
Jantzen, P. T., Connor, K. E., DiCarlo, G., Wenk, G. L., Wallace, J. L., Rojiani, A. M., Coppola, D., Morgan, D., & Gordon, M. N. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-06-02246.2002 · Cited by 341 · cited 1×
“In support of this, Jantzen and colleagues [127] suggest that microglial activation may be beneficial based on results of their studies of a nitric oxide-releasing NSAID, NCX-2216.”
Background
Immunology and immunotherapy of Alzheimer's disease
Weiner, H. L., & Frenkel, D. (2006) · Nature Reviews Immunology · doi:10.1038/nri1843 · Cited by 335
Self-citation
Microglia and Alzheimer's disease pathogenesis
Streit, W. J. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20093 · Cited by 335 · cited 4×
“Microglia accumulate in plaques containing A fibrils, but not in plaques containing amorphous non-fibrillar amyloid [47].”
BackgroundInfluential
Up-Regulated Production and Activation of the Complement System in Alzheimer's Disease Brain
Yasojima, K., Schwab, C., McGeer, E. G., & McGeer, P. L. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65340-0 · Cited by 328 · cited 1×
“hippocampus and cortex), C1q mRNA level is increased up to 80-fold compared to control levels [27].”
Background
Role of complement in neurodegeneration and neuroinflammation
Bonifati, D. M., & Kishore, U. (2006) · Molecular Immunology · doi:10.1016/j.molimm.2006.03.007 · Cited by 314 · cited 2×
“The complement system provides an innate immune response against pathogenic features and contributes to the local inflammatory response triggered by A deposition and NFT in AD [17, 22].”
Background
Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice
Heneka, M. T., Sastre, M., Dumitrescu-Ozimek, L., Dewachter, I., Walter, J., Klockgether, T., & Van Leuven, F. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-22 · Cited by 309 · cited 1×
“It is possible, however, that small soluble aggregates of A trigger local activation of glial cells, as suggested by a recent study of the young thymus cell antigen 1 (Thy1)-APP mice that had not yet developed A deposits [48].”
The LPS receptor (CD14) links innate immunity with Alzheimer's disease
Fassbender, K., Walter, S., Kühl, S., Landmann, R., Ishii, K., Bertsch, T., Stalder, A. K., Muehlhauser, F., Liu, Y., Ulmer, A. J., et al. (2004) · The FASEB Journal · doi:10.1096/fj.03-0364fje · Cited by 307
Toll‐like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators
Bsibsi, M., Persoon-Deen, C., Verwer, R. W. H., Meeuwsen, S., Ravid, R., & van Noort, J. M. (2006) · Glia · doi:10.1002/glia.20328 · Cited by 301
Immunohistochemical Study of the β-Chemokine Receptors CCR3 and CCR5 and Their Ligands in Normal and Alzheimer's Disease Brains
Xia, M., Qin, S., Wu, L., Mackay, C. R., & Hyman, B. T. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65542-3 · Cited by 300
Alzheimer's β-Amyloid Peptides Compete for Insulin Binding to the Insulin Receptor
Xie, L., Helmerhorst, E., Taddei, K., Plewright, B., van Bronswijk, W., & Martins, R. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-10-j0001.2002 · Cited by 291 · cited 1×
“Soluble A can be directly bound by microglial cell receptors, including the heparan sulphate proteoglycans (HSPGs) [57], insulin receptors [58], proteinase inhibitor (serpin)–enzyme complex receptor (SEC-R) [59] and an accumulation of the receptor for advanced glycation end products (RAGE) [60, 61].”
Background
Amyloid β42Activates a G-Protein-Coupled Chemoattractant Receptor, FPR-Like-1
Le, Y., Gong, W., Tiffany, H. L., Tumanov, A. V., Nedospasov, S. A., Shen, W., Dunlop, N. M., Gao, J., Murphy, P. M., Oppenheim, J. J., et al. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-02-j0003.2001 · Cited by 278
Advanced glycation endproducts in ageing and Alzheimer's disease
Münch, G. W., Thome, J., Foley, P. B., Schinzel, R., & Riederer, P. F. (1997) · Brain Research Reviews · doi:10.1016/s0165-0173(96)00016-1 · Cited by 278 · cited 14×
“Lue LF,Walker DG, Brachova L, Beach TG, Rogers J, Schmidt AM, Stern DM, Yan SD. Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer’s disease: identification of a cellular activation mechanism.”
BackgroundInfluential
Evidence That Aging And Amyloid Promote Microglial Cell Senescence
Flanary, B. E., Sammons, N. W., Nguyen, C., Walker, D., & Streit, W. J. (2007) · Rejuvenation Research · doi:10.1089/rej.2006.9096 · Cited by 272 · cited 2×
“Furthermore, a recent study reports that microglial cells exhibit significant telomere shortening and a reduction of telomerase activity in normal aging rats [66], and that in humans there is a tendency toward microglial cell telomere shortening with a presence of dementia [66].”
Background
Chemokines/chemokine receptors in the central nervous system and Alzheimer's disease
Xia, M., & Hyman, B. T. (1999) · Journal of NeuroVirology · doi:10.3109/13550289909029743 · Cited by 269 · cited 2×
“Several chemokines and chemokine receptors have been found to be up-regulated in the AD brain [32].”
Background
Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes: in vitro ERK1/2 activation and role in Alzheimer’s disease
Xia, M. Q., Bacskai, B. J., Knowles, R. B., Qin, S. X., & Hyman, B. T. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00285-x · Cited by 269
In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis
Sheng, J. G., Ito, K., Skinner, R. D., Mrak, R. E., Rovnaghi, C. R., van Eldik, L. J., & Griffin, W. S. T. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(96)00104-2 · Cited by 269 · cited 3×
“Edwards MM, Robinson SR. TNF alpha affects the expression of GFAP and S100B: implications for Alzheimer’s disease.”
Background
Microglia and neuroprotection: implications for Alzheimer's disease
Streit, W. J. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.12.013 · Cited by 262 · cited 1×
“In addition to their innate ability to phagocytose and clear A , glial cells can also be activated to promote the clearance of A and prevent neuronal death in AD [65, 117, 122, 123] (Table 1).”
Background
Astrocytes Regulate Microglial Phagocytosis of Senile Plaque Cores of Alzheimer's Disease
DeWitt, D. A., Perry, G., Cohen, M., Doller, C., & Silver, J. (1998) · Experimental Neurology · doi:10.1006/exnr.1997.6738 · Cited by 261 · cited 1×
“In AD, activated astrocytes can contain A fragments, providing further evidence of their role in A degradation [90].”
Background
Inflammation and therapeutic vaccination in CNS diseases
Weiner, H. L., & Selkoe, D. J. (2002) · Nature · doi:10.1038/nature01325 · Cited by 253
Activation of alpha7 nicotinic acetylcholine receptor by nicotine selectively up-regulates cyclooxygenase-2 and prostaglandin E2 in rat microglial cultures.
Simone, R. D., Ajmone‐Cat, M. A., Carnevale, D., & Minghetti, L. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-4 · Cited by 251
Leukemia inhibitory factor is expressed by the preimplantation uterus and selectively blocks primitive ectoderm formation in vitro.
Shen, M. M., & Leder, P. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.17.8240 · Cited by 250
Identification of monocyte chemoattractant protein‐1 in senile plaques and reactive microglia of Alzheimer's disease
ISHIZUKA, K., KIMURA, T., IGATA‐YI, R., KATSURAGI, S., TAKAMATSU, J., & MIYAKAWA, T. (1997) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.1997.tb02375.x · Cited by 245 · cited 4×
“Furthermore, an astrocytic response to IL-1 and TNF- results in an elevation of colony stimulating factor 1 (CSF-1) [86], granulocyte-macrophage CSF (GM-CSF) [86], granulocyte CSF (G-CSF) [86], MCP-1 and MIP-1 [33, 87], which can lead to the recruitment of microglial cells to A plaques [88].”
BackgroundInfluential
Differences in the Mode of Phagocytosis with Fc and C3 Receptors in Macrophages
Kaplan, G. (1977) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.1977.tb02153.x · Cited by 244 · cited 1×
“Engagement of the FcR by immune IgG initiates phagocytosis [117, 128, 129], which is characterized by an extension of pseudopodia and an envelopment of the phagocytic target by a mechanism of tyrosine kinases, Rac and Cdc42 [130].”
Background
IgG-Assisted Age-Dependent Clearance of Alzheimer's Amyloid β Peptide by the Blood–Brain Barrier Neonatal Fc Receptor
Deane, R., Sagare, A. P., Hamm, K., Parisi, M., LaRue, B., Guo, H., Wu, Z., Holtzman, D. M., & Zloković, B. V. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3697-05.2005 · Cited by 238
Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factor in situ
Aharoni, R., Kayhan, B., Eilam, R., Sela, M., & Arnon, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2336171100 · Cited by 233 · cited 1×
“Recent reports [143, 144] suggest that this can be achieved in APP-transgenic mice by immunizing them with glatiramer acetate (GA) [145], which is a random amino acid copolymer of alanine, lysine, glutamic acid and tyrosine used for the treatment of multiple sclerosis that induces both Th2- and Th3-cell response.”
Background
Intrahippocampal LPS injections reduce AÎ² load in APP+PS1 transgenic mice
DiCarlo, G. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00292-5 · Cited by 223
Glial activation in Alzheimer's disease: the role of AÎ² and its associated proteins
Meda, L. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00307-4 · Cited by 222 · cited 1×
“Astrocyte activation seems to be particularly prominent around A deposits both in the brain parenchyma and in the cerebrovasculature [63].”
Background
Activity-Dependent Neuroprotective Protein Snippet NAP Reduces Tau Hyperphosphorylation and Enhances Learning in a Novel Transgenic Mouse Model
Vulih-Shultzman, I., Pinhasov, A., Mandel, S., Grigoriadis, N., Touloumi, O., Pittel, Z., & Gozes, I. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.129551 · Cited by 219 · cited 3×
“Research of the activity-dependent neuroprotective protein (ADNP), a gene product essential for brain formation, shows that ADNP knockout is embryonic lethal and that an ADNP partial deficiency results in cognitive deficits that are paralleled by tau hyperphosphorylation [162].”
BackgroundMethod
Therapies for Alzheimer's disease
Melnikova, I. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2314 · Cited by 219 · cited 2×
“Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd phase II clinical trial of patients with AD [137, 138].”
Background
Increased S100β neurotrophic activity in Alzheimer's disease temporal lobe
Marshak, D. R., Pesce, S. A., Stanley, L. C., & Griffin, W. S. T. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90002-f · Cited by 218
Role of CD40 ligand in amyloidosis in transgenic Alzheimer's mice
Tan, J., Town, T., Crawford, F., Mori, T., DelleDonne, A., Crescentini, R., Obregon, D., Flavell, R. A., & Mullan, M. J. (2002) · Nature Neuroscience · doi:10.1038/nn968 · Cited by 217 · cited 3×
“This finding suggests several possible mechanisms underlying mitigation of AD pathology in response to CD40L and validates the CD40–CD40L interaction as a target for therapeutic intervention in AD [54, 118] (Table 1).”
Background
Activation of Toll-like Receptor 2 on Microglia Promotes Cell Uptake of Alzheimer Disease-associated Amyloid β Peptide
Chen, K., Iribarren, P., Hu, J., Chen, J., Gong, W., Cho, E. H., Lockett, S., Dunlop, N. M., & Wang, J. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508125200 · Cited by 214
Amyloid-β Immunization Effectively Reduces Amyloid Deposition in FcRγ-/-Knock-Out Mice
Das, P., HOWARD, V. G., Loosbrock, N., Dickson, D. W., Murphy, M. P., & Golde, T. E. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-24-08532.2003 · Cited by 213
Aβ-degrading enzymes: modulators of Alzheimer's disease pathogenesis and targets for therapeutic intervention
Eckman, C. B., & Eckman, E. A. (2005) · Biochemical Society Transactions · doi:10.1042/bst20051101 · Cited by 211 · cited 2×
“Genetic studies have also shown that IDE and NEP gene variations are associated with the clinical symptoms of AD [151, 152].”
Background
The role of complement and activated microglia in the pathogenesis of Alzheimer's disease
Eikelenboom, P., & Veerhuis, R. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(96)00108-x · Cited by 206 · cited 1×
“Furthermore, A fibril interacts with numerous microglial membrane receptors including scavenger receptor A (SRA) [20, 52] and B [20], CD36 [53], CD40 [54], 6/ 1 integrinCD36-CD47 complex [55] and complement receptors [56] (Table 1).”
Background
Microglial activation facilitates Aβ plaque removal following intracranial anti-Aβ antibody administration
Wilcock, D. M., Munireddy, S. K., Rosenthal, A., Ugen, K. E., Gordon, M. N., & Morgan, D. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.09.015 · Cited by 202
Lipopolysaccharides from atherosclerosis-associated bacteria antagonize TLR4, induce formation of TLR2/1/CD36 complexes in lipid rafts and trigger TLR2-induced inflammatory responses in human vascular endothelial cells
Triantafilou, M., Gamper, F. G. J., Lepper, P. M., Mouratis, M. A., Schumann, C., Harokopakis, E., Schifferle, R. E., Hajishengallis, G., & Triantafilou, K. (2007) · Cellular Microbiology · doi:10.1111/j.1462-5822.2007.00935.x · Cited by 202
Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears β-amyloid in a mouse model of Alzheimer disease
Frenkel, D., Maron, R., Burt, D. S., & Weiner, H. L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23241 · Cited by 189 · cited 6×
“Protollin might act by stimulating microglial cells both through LPS via TLR4 and through Por B, which makes up 70% of the proteosome protein and activates antigen-presenting cells via TLR2 [143].”
BackgroundInfluentialSelf-citation
Loss of synaptophysin-like immunoreactivity in the hippocampal formation is an early phenomenon in alzheimer's disease
Heinonen, O., Soininen, H., Sorvari, H., Kosunen, O., Paljärvi, L., Koivisto, E., & Riekkinen, P. J. (1995) · Neuroscience · doi:10.1016/0306-4522(94)00422-2 · Cited by 188
In vivo detection of microglial activation in frontotemporal dementia
Cagnin, A., Rossor, M., Sampson, E. L., MacKinnon, T., & Banati, R. B. (2004) · Annals of Neurology · doi:10.1002/ana.20332 · Cited by 187 · cited 1×
“Furthermore, studies found activated microglia in vivo (in the brains of AD patients), by using positron emission tomography and 11C-PK111995, which is a marker of peripheral benzodiazepine binding sites that are upregulated on the activated microglia [49, 50].”
Background
S100β protein expression in Alzheimer disease: Potential role in the pathogenesis of neuritic plaques
Sheng, J. G., Mrak, R. E., & Griffin, W. S. T. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490390406 · Cited by 184 · cited 1×
“Tissue levels of S100B correlates with the number of neuritic plaques in the temporal lobe [78, 83] but not in the cerebellum where there is no evidence of neuritic plaques, suggesting a correlation between AD pathology and activated astrocyte.”
Background
Endogenous brain cytokine mRNA and inflammatory responses to lipopolysaccharide are elevated in the Tg2576 transgenic mouse model of Alzheimer’s disease
Sly, L. M., KRZESICKI, R. F., Brashler, J. R., Buhl, A.-L., McKinley, D. D., Carter, D. B., & Chin, J. E. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00730-4 · Cited by 180 · cited 1×
“In these studies, LPS was given intravenously [155], intracerebroventricularly [156] or intraperitoneally [157].”
Method
Chemokines and Chemokine Receptors in Neurological Disease: Raise, Retain, or Reduce?
Savarin-Vuaillat, C., & Ransohoff, R. M. (2007) · Neurotherapeutics · doi:10.1016/j.nurt.2007.07.004 · Cited by 177
Modeling microglial activation in Alzheimer's disease with human postmortem microglial cultures
Lue, L. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00311-6 · Cited by 169 · cited 1×
“Microglia cultured from rapid autopsies of AD and non-demented patients reveal an increased expression of chemokines such as IL-8, monocyte chemoattractant protein-1 (MCP-1; also known as CCL2) and macrophage inflammatory MIP-1 (CCL3) after experimental exposure to A [70].”
Background
In vivo visualization of activated glia by[11C] (R)-PK11195-PET following herpes encephalitis reveals projected neuronal damage beyond the primary focal lesion
Cagnin, A. (2001) · Brain · doi:10.1093/brain/124.10.2014 · Cited by 169 · cited 1×
“Furthermore, studies found activated microglia in vivo (in the brains of AD patients), by using positron emission tomography and 11C-PK111995, which is a marker of peripheral benzodiazepine binding sites that are upregulated on the activated microglia [49, 50].”
Background
The HHQK Domain of β-Amyloid Provides a Structural Basis for the Immunopathology of Alzheimer's Disease
Giulian, D., Haverkamp, L. J., Yu, J., Karshin, W. L., Tom, D., Li, J., Kazanskaia, A., Kirkpatrick, J. B., & Roher, A. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.45.29719 · Cited by 161 · cited 1×
“Soluble A can be directly bound by microglial cell receptors, including the heparan sulphate proteoglycans (HSPGs) [57], insulin receptors [58], proteinase inhibitor (serpin)–enzyme complex receptor (SEC-R) [59] and an accumulation of the receptor for advanced glycation end products (RAGE) [60, 61].”
Background
Expression of Scavenger Receptors in Glial Cells
Alarcón, R., Fuenzalida, C., Santibáñez, M., & Rommy von Bernhardi, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414686200 · Cited by 159
Time-dependent reduction in Aβ levels after intracranial LPS administration in APP transgenic mice
Herber, D. L., Roth, L. M., Wilson, D. H., Wilson, N., Mason, J. E., Morgan, D., & Gordon, M. N. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.07.007 · Cited by 151 · cited 1×
“However, others studies showed enhanced A clearance through microglial cell activation when LPS was injected intrahippocampally [158, 159] or intracranial [160] to older APP-transgenic mice.”
Background
Oral vaccination with a viral vector containing Aβ cDNA attenuates age‐related Aβ accumulation and memory deficits without causing inflammation in a mouse Alzheimer model
Mouri, A., Noda, Y., Hara, H., Mizoguchi, H., Tabira, T., & Nabeshima, T. (2007) · The FASEB Journal · doi:10.1096/fj.06-7685com · Cited by 149
Apolipoprotein E-Containing Lipoproteins Protect Neurons from Apoptosis via a Signaling Pathway Involving Low-Density Lipoprotein Receptor-Related Protein-1
Hayashi, H., Campenot, R. B., Vance, D. E., & Vance, J. E. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5471-06.2007 · Cited by 146 · cited 1×
“In addition, binding APOE-LPs to LRP initiates the prevention of neuronal apoptosis [102].”
Background
Astroglial overproduction of TGF-β1 enhances inflammatory central nervous system disease in transgenic mice
Wyss‐Coray, T., Borrow, P., Brooker, M. J., & Mucke, L. (1997) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(97)00049-0 · Cited by 145 · cited 1×
“Overexpression of TGF- 1 by the promoter of the GFAP, a specific marker of astrocytes, within the CNS can result in cerebrovascular amyloid and enhance immune cell infiltration from peripherally triggered autoimmune responses [107] (Fig.”
Background
NAP: Research and Development of a Peptide Derived from Activity-Dependent Neuroprotective Protein (ADNP)
Gozes, I., Morimoto, B. H., Tiong, J., Fox, A. W., Sutherland, K., Dangoor, D., Holser-Cochav, M., Vered, K., Newton, P. E., Aisen, P. S. S., et al. (2006) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2005.tb00053.x · Cited by 144 · cited 1×
“The use of NAP may open up new horizons in research and development of protective compounds to both neurons and the supporting glial cells [166, 167].”
Background
Microglia-Neuron Interaction in Inflammatory and Degenerative Diseases: Role of Cholinergic and Noradrenergic Systems
Minghetti, L., Carnevale, D., & Simone, R. D. (2007) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152707783399193 · Cited by 144
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
Autoantibodies to amyloid-? and Alzheimer's disease
Hyman, B. T., Smith, C. R., Buldyrev, I., Whelan, C. M., Brown, H., Tang, M., & Mayeux, R. P. (2001) · Annals of Neurology · doi:10.1002/ana.1061 · Cited by 144
Glia Proinflammatory Cytokine Upregulation as a Therapeutic Target for Neurodegenerative Diseases: Function‐Based and Target‐Based Discovery Approaches
Eldik, L. J. V., Thompson, W. L., Ranaivo, H. R., Behanna, H. A., & Watterson, D. M. (2007) · International review of neurobiology · doi:10.1016/s0074-7742(07)82015-0 · Cited by 141 · cited 1×
“Activated microglia represent the major source of inflammatory factors in the brain in neurodegenerative disorders such as AD [46].”
Background
Microglial Phagocytosis of Apoptotic Inflammatory T Cells Leads to Down-Regulation of Microglial Immune Activation
Magnus, T., Chan, A., Grauer, O. M., Toyka, K. V., & Gold, R. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.9.5004 · Cited by 141
Amyloid β‐Peptide Induces Cell Monolayer Albumin Permeability, Impairs Glucose Transport, and Induces Apoptosis in Vascular Endothelial Cells
Blanc, E. M., Toborek, M., Mark, R. J., Hennig, B., & Mattson, M. P. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68051870.x · Cited by 141
Complement Component C1q Modulates the Phagocytosis of Aβ by Microglia
Webster, S. D., Yang, A. J., Margol, L., Garzon-Rodriguez, W., Glabe, C. G., & Tenner, A. J. (2000) · Experimental Neurology · doi:10.1006/exnr.1999.7260 · Cited by 138 · cited 1×
“Complement components may modulate the phagocytosis of A by microglia [150].”
Background
A Femtomolar Acting Octapeptide Interacts with Tubulin and Protects Astrocytes against Zinc Intoxication
Divinski, I., Mittelman, L. A., & Gozes, I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403197200 · Cited by 136 · cited 1×
“Structure-activity studies identified a short peptide sequence in ADNP, known as a neuronal microtubule-interacting agent (NAP; amino acid sequence NAPVSIPQ), which mimics the neuroprotective activity of the parent protein and crosses the BBB after systemic or intranasal administration and can support the integrity of…”
Background
Expression of CD40 in the brain of Alzheimer’s disease and other neurological diseases
Togo, T., Akiyama, H., Kondo, H., Ikeda, K., Kato, M., Iseki, E., & Kosaka, K. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02984-x · Cited by 131
Interleukin-8 receptor B immunoreactivity in brain and neuritic plaques of Alzheimer's disease.
Xia, M., Qin, S., McNamara, M. J., Mackay, C. R., & Hyman, B. T. (1997) · Europe PMC (PubMed Central) · Cited by 131
Tumor necrosis factor α and transforming growth factor β upregulate astrocyte expression of monocyte chemoattractant protein-1
Hurwitz, A. A., Lyman, W. D., & Herman, J. W. (1995) · Journal of Neuroimmunology · doi:10.1016/0165-5728(95)00011-p · Cited by 130
Characterization of microglial responses to Staphylococcus aureus: effects on cytokine, costimulatory molecule, and Toll-like receptor expression
Kielian, T., Mayes, P. M., & Kielian, M. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00216-3 · Cited by 129
Anti‐Inflammatory Drugs in the Fight against Alzheimer's Diseasea
McGeer, P. L., & McGeer, E. G. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34421.x · Cited by 123 · cited 1×
“Epidemiological studies have documented a reduced prevalence of AD among users of nonsteroidal anti-inflammatory drugs (NSAIDs) [124, 125].”
Background
Scavenger receptor class B type I (SR-BI) mediates adhesion of neonatal murine microglia to fibrillar β-amyloid
Husemann, J., Loike, J. D., Kodama, T., & Silverstein, S. C. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00239-9 · Cited by 122
The scavenger receptor MARCO mediates cytoskeleton rearrangements in dendritic cells and microglia
Granucci, F., Petralia, F., Urbano, M., Citterio, S., Tota, F. P. D., Santambrogio, L., & Ricciardi‐Castagnoli, P. (2003) · Blood · doi:10.1182/blood-2002-12-3651 · Cited by 121
CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid β‐peptide
Townsend, K. P., Town, T., Mori, T., Lue, L., Shytle, D., Sanberg, P. R., Morgan, D., Fernandez, F., Flavell, R. A., & Tan, J. (2005) · European Journal of Immunology · doi:10.1002/eji.200425585 · Cited by 121 · cited 11×
“Suo Z, Tan J, Placzek A, Crawford F, Fang C, Mullan M. Alzheimer’s beta-amyloid peptides induce inflammatory cascade in human vascular cells: the roles of cytokines and CD40.”
BackgroundInfluential
Expression of Scavenger Receptor Class B, Type I, by Astrocytes and Vascular Smooth Muscle Cells in Normal Adult Mouse and Human Brain and in Alzheimer’s Disease Brain
Husemann, J., & Silverstein, S. C. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64030-8 · Cited by 119
Neuroinflammation‐induced acceleration of amyloid deposition in the APPV717F transgenic mouse
Qiao, X., Cummins, D. J., & Paul, S. M. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01666.x · Cited by 119 · cited 1×
“In these studies, LPS was given intravenously [155], intracerebroventricularly [156] or intraperitoneally [157].”
Method
Binding Sites of Amyloid β-Peptide in Cell Plasma Membrane and Implications for Alzheimers Disease
Verdier, Y., & Penke, B. (2004) · Current Protein and Peptide Science · doi:10.2174/1389203043486937 · Cited by 118 · cited 1×
“Targeting SRs can mediate the activation of glial cells towards A clearance [147].”
Background
The role of intracellular amyloid β in Alzheimer's disease
Li, M. C., Chen, L., Lee, D. H. S., Yu, L., & Zhang, Y. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.08.002 · Cited by 118
Chemokines in serum and cerebrospinal fluid of Alzheimer's disease patients
Galimberti, D., Schoonenboom, N. S. M., Scarpini, E. A., & Scheltens, P. (2003) · Annals of Neurology · doi:10.1002/ana.10531 · Cited by 116 · cited 1×
“Furthermore, increased levels of MCP-1 and IL-8/CXCL8 can be found in the CSF in the majority of AD patients, therefore chemokines in the CSF may provide a useful diagnosis for AD progression [35].”
Background
Alzheimer's β-amyloid peptides induce inflammatory cascade in human vascular cells: the roles of cytokines and CD40
Suo, Z., Tan, J., Placzek, A., Crawford, F., Fang, C., & Mullan, M. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00780-x · Cited by 116
Cerebral amyloid angiopathy: Pathogenesis and effects on the ageing and Alzheimer brain
Weller, R. O., & Nicoll, J. A. R. (2003) · Neurological Research · doi:10.1179/016164103101202057 · Cited by 114 · cited 2×
“The deposits cause intraparenchymal and subarachnoid bleeding, which leads to haemorrhage, stroke with hemosiderin deposits, multiple infarcts and cognitive impairment [109] (Fig.”
Background
Alzheimer's disease and soluble Aβ
Wısnıewskı, T., Ghiso, J. A., & Frangione, B. (1994) · Neurobiology of Aging · doi:10.1016/0197-4580(94)90105-8 · Cited by 112
Identification of FcγRI, II and III on normal human brain ramified microglia and on microglia in senile plaques in Alzheimer's disease
Peress, N. S., Fleit, H. B., Perillo, E., Kuljiš, R. O., & Pezzullo, C. (1993) · Journal of Neuroimmunology · doi:10.1016/0165-5728(93)90060-c · Cited by 111
Identification of CD40 ligand in Alzheimer’s disease and in animal models of Alzheimer’s disease and brain injury
Calingasan, N. Y., Erdely, H. A., & Altar, C. A. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00246-9 · Cited by 109
Role of Formyl Peptide Receptor–Like 1 (FPRL1/FPR2) in Mononuclear Phagocyte Responses in Alzheimer Disease
Iribarren, P., Zhou, Y., Hu, J., Le, Y., & Wang, J. M. (2005) · Immunologic Research · doi:10.1385/ir:31:3:165 · Cited by 108
Evidence of a Role for Lactadherin in Alzheimer's Disease
Boddaert, J., Kinugawa, K., Lambert, J., Boukhtouche, F., Zoll, J., Merval, R., Blanc‐Brude, O., Mann, D. M. A., Berr, C., Vilar, J., et al. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060664 · Cited by 108 · cited 2×
“One study found that there is less lactadherin found in the brains of AD patients [149].”
Background
Microglial transplantation increases amyloid‐β clearance in Alzheimer model rats
Takata, K., Kitamura, Y., Yanagisawa, D., Morikawa, S., Morita, M., Inubushi, T., Tsuchiya, D., Chishiro, S., Saeki, M., Taniguchi, T., et al. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.01.009 · Cited by 106
Antibody-Mediated Phagocytosis of the Amyloid β-Peptide in Microglia Is Differentially Modulated by C1q
Webster, S. D., Galvan, M. D., Ferran, E., Garzon-Rodriguez, W., Glabe, C. G., & Tenner, A. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.12.7496 · Cited by 104 · cited 1×
“Thereby activation of the complement system can lead to increased phagocytosis of A by microglial cells [30].”
Background
A nontransgenic mouse model shows inducible amyloid-β (Aβ) peptide deposition and elucidates the role of apolipoprotein E in the amyloid cascade
Dolev, I., & Michaelson, D. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404458101 · Cited by 102
Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease
Quinn, J. (2003) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(03)00037-7 · Cited by 102 · cited 1×
“However, others studies showed enhanced A clearance through microglial cell activation when LPS was injected intrahippocampally [158, 159] or intracranial [160] to older APP-transgenic mice.”
Background
The Serpin-Enzyme Complex Receptor Recognizes Soluble, Nontoxic Amyloid-β Peptide but Not Aggregated, Cytotoxic Amyloid-β Peptide
Boland, K., Behrens, M. I., Choi, D. W., Manias, K., & Perlmutter, D. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.18032 · Cited by 91 · cited 1×
“Soluble A can be directly bound by microglial cell receptors, including the heparan sulphate proteoglycans (HSPGs) [57], insulin receptors [58], proteinase inhibitor (serpin)–enzyme complex receptor (SEC-R) [59] and an accumulation of the receptor for advanced glycation end products (RAGE) [60, 61].”
Background
Development of a safe oral Aβ vaccine using recombinant adeno-associated virus vector for Alzheimer's disease
Hara, H., Monsonego, A., Yuasa, K., Adachi, K., Xiao, X., Takeda, S., Takahashi, K., Weiner, H. L., & Tabira, T. (2004) · Journal of Alzheimer s Disease · doi:10.3233/jad-2004-6504 · Cited by 90
Genetic factors in Alzheimer's disease: A review of recent advances
Levy‐Lahad, E., & Bird, T. D. (1996) · Annals of Neurology · doi:10.1002/ana.410400604 · Cited by 86 · cited 2×
“The protective effect was greater for ApoE3 than for ApoE4, the expression of which is a risk factor for AD [103].”
Background
Reduction of β-amyloid plaques in brain of transgenic mouse model of Alzheimer’s disease by EFRH-phage immunization
Frenkel, D., Dewachter, I., LEUVEN, F. V., & Solomon, B. (2003) · Vaccine · doi:10.1016/s0264-410x(02)00609-6 · Cited by 85
Self-citation
TGF-β Pathway as a Potential Target in Neurodegeneration and Alzheimers
Wyss-Coray, T. (2006) · Current Alzheimer Research · doi:10.2174/156720506777632916 · Cited by 85 · cited 2×
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Background
Human antibodies reactive with beta-amyloid protein in Alzheimer's disease.
Gaskin, F., Finley, J., Fang, Q., Xu, S., & Fu, S. M. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.4.1181 · Cited by 82 · cited 14×
“Glial cells secrete the LRP ligand, ApoE-containing lipoproteins (ApoE-LPs) [101], which have an important role in lipid homeostasis in the CNS. Glia-derived APOELPs also promote synaptogenesis and stimulate axon growth of CNS neurons [101].”
BackgroundInfluential
Non-steroidal Anti-inflammatory Drugs and Cyclooxygenase in Alzheimer s Disease
Hoozemans, J. J. M., Veerhuis, R., Rozemüller, A. J. M., & Eikelenboom, P. (2003) · Current Drug Targets · doi:10.2174/1389450033490902 · Cited by 81 · cited 2×
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Structure-function studies of the receptors for complement C1q
McGreal, E. P., & Gasque, P. (2002) · Biochemical Society Transactions · doi:10.1042/bst0301010 · Cited by 80
Effect of IL‐6 polymorphism on risk of Alzheimer disease: Genotype‐phenotype association study in Japanese cases
Shibata, N., Ohnuma, T., Takahashi, T., Baba, H., Ishizuka, T., Ohtsuka, M., Ueki, A., Nagao, M., & Arai, H. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10417 · Cited by 80 · cited 5×
“Isolated microglia from postmortem AD and control (non-demented) patients’ brain tissue exhibit pro-inflammatory cytokine expression profiles, in the form of a significantly increased expression of IL-1 , TNF- , IL-6 and IL-12, following an exposure to A peptides.”
BackgroundInfluential
TNF alpha affects the expression of GFAP and S100B: implications for Alzheimer’s disease
Edwards, M. M., & Robinson, S. R. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-006-0479-5 · Cited by 79 · cited 1×
“Astrocyte activity is marked by hypertrophy [79], resulting in an expression of proteins such as glial fibrillary acidic protein (GFAP), S100B [78, 80], adhesion molecules and antigen presenting capabilities, including MHC antigens [81, 82].”
Background
Potential role of the formyl peptide receptor-like 1 (FPRL1) in inflammatory aspects of Alzheimer's disease
Cui, Y., Le, Y., Yazawa, H., Gong, W., & Wang, J. M. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.4.628 · Cited by 79
The femtomolar-acting NAP interacts with microtubules: Novel aspects of astrocyte protection
Gozes, I., & Divinski, I. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2004-6s605 · Cited by 77 · cited 1×
“The use of NAP may open up new horizons in research and development of protective compounds to both neurons and the supporting glial cells [166, 167].”
Background
Microglial interaction with β‐amyloid: Implications for the pathogenesis of Alzheimer's disease
Bamberger, M. E., & Landreth, G. E. (2001) · Microscopy Research and Technique · doi:10.1002/jemt.1121 · Cited by 74
Mechanisms of cell death in Alzheimer disease — immunopathology
McGeer, P. L., & McGeer, E. G. (1998) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-7508-8_15 · Cited by 73 · cited 1×
“Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd provide a specific mechanism for recruiting reactive glial cells to the sites of the A plaque and lead to inflammatory events, neuronal dysfunction and degeneration through production of pro-inflammatory cytokines and ox…”
Background
Astrocytes and intracerebral immune responses
Frohman, E. M., van den Noort, S., & Gupta, S. (1989) · Journal of Clinical Immunology · doi:10.1007/bf00917121 · Cited by 72 · cited 1×
“Astrocyte activity is marked by hypertrophy [79], resulting in an expression of proteins such as glial fibrillary acidic protein (GFAP), S100B [78, 80], adhesion molecules and antigen presenting capabilities, including MHC antigens [81, 82].”
Background
Immunohistochemical and Ultrastructural Studies
Kikuchi, A., Akiyama, M., Hanyaku, H., Shimizu, H., Naka, W., & Nishikawa, T. (1993) · American Journal of Dermatopathology · doi:10.1097/00000372-199302000-00003 · Cited by 71
Fas Ligand (CD95L) Protects Neurons Against Perforin- Mediated T Lymphocyte Cytotoxicity
Medana, I. M., Li, Z., Flügel, A., Tschopp, J., Wekerle, H., & Neumann, H. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.2.674 · Cited by 71
The role of apolipoprotein E in lipid metabolism in the central nervous system
Han, X. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4009-z · Cited by 69 · cited 2×
“Glial cells secrete the LRP ligand, ApoE-containing lipoproteins (ApoE-LPs) [101], which have an important role in lipid homeostasis in the CNS.”
Background
Neuroglial networks: Neurons and glia talk to each other
Haydon, P. G. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00708-9 · Cited by 66 · cited 1×
“Astrocytes are the most abundant cells in the CNS and play an important role in the homeostasis and maintenance of the brain [74, 75].”
Background
Laminin inhibits amyloid-β-peptide fibrillation
Bronfman, F. C., Garrido, J., Alvarez, A. R., Morgan, C., & Inestrosa, N. C. (1996) · Neuroscience Letters · doi:10.1016/s0304-3940(96)13147-5 · Cited by 62
Inflammation in the nervous system — Physiological and pathophysiological aspects
Schultzberg, M., Lindberg, C., Aronsson, Å. F., Hjorth, E., Spulber, S. D., & Oprica, M. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.05.050 · Cited by 62 · cited 1×
“Pro-inflammatory cytokines, such as interleukin1 (IL-1 / [36, 37], tumour necrosis factor- (TNF- ) [38] and IL-6 [39], may play an important role in AD pathology and lead to an increased production of inducible nitric oxide synthase (iNOS), neuronal stress and further neuronal dysfunction and death [40].”
Background
In Vitro Evidence That β-Amyloid Peptide 1–40 Diffuses Across the Blood–Brain Barrier and Affects Its Permeability
Strazielle, N., Ghersi‐Egea, J., Ghiso, J. A., Dehouck, M., Frangione, B., Patlak, C. S., Fenstermacher, J. D., & Gorevic, P. D. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.1.29 · Cited by 60 · cited 1×
“A increases endothelial monolayer permeability [111, 112], stimulates secretion of inflammatory cytokines [113] and up-regulates vascular cell adhesion molecules (Fig.”
Background
Protollin™: a novel adjuvant for intranasal vaccines
Jones, T., Cyr, S. L., Allard, F., Bellerose, N., Lowell, G. H., & Burt, D. S. (2004) · Vaccine · doi:10.1016/j.vaccine.2004.03.035 · Cited by 52 · cited 1×
“Furthermore, nasal administration of a proteosome-based adjuvant (Protollin) [161], composed of purified outer membrane proteins of Neisseria meningitides and LPS, also reduces A in”
Background
Gliosis in human brain: relationship to size but not other properties of astrocytes
da Cunha, A., Jefferson, J. J., Tyor, W. R., Glass, J. D., Jannotta, F. S., & Vitković, L. (1993) · Brain Research · doi:10.1016/0006-8993(93)90415-j · Cited by 51 · cited 1×
“Astrocyte activity is marked by hypertrophy [79], resulting in an expression of proteins such as glial fibrillary acidic protein (GFAP), S100B [78, 80], adhesion molecules and antigen presenting capabilities, including MHC antigens [81, 82].”
Background
Genetically-targeted and conditionally-regulated ablation of astroglial cells in the central, enteric and peripheral nervous systems in adult transgenic mice1Published on the World Wide Web on 7 June 1999.1
Sofroniew, M. V., Bush, T. G., Blumauer, N., Kruger, L., Mucke, L., & Johnson, M. H. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01639-x · Cited by 48 · cited 1×
“Astrocytes are the most abundant cells in the CNS and play an important role in the homeostasis and maintenance of the brain [74, 75].”
Background
Possible role of scavenger receptor SRCL in the clearance of amyloid‐βin Alzheimer's disease
Nakamura, K. D., Ohya, W., Funakoshi, H., Sakaguchi, G., Kato, A., Takeda, M., Kudo, T., & Nakamura, T. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20992 · Cited by 46 · cited 1×
“The presence of a large number of SRCL together with A double-positive particles in the intracellular compartments of reactive astrocytes and vascular or perivascular cells in APP mice suggests a role for SRCL in A clearance [148].”
Background
Selective localization of gelatinase A, an enzyme degrading ?-amyloid protein, in white matter microglia and in Schwann cells
Yamada, T., Miyazaki, K., Koshikawa, N., Takahashi, M., Akatsu, H., & Yamamoto, T. (1995) · Acta Neuropathologica · doi:10.1007/bf00309334 · Cited by 45 · cited 1×
“Glial cells can also degrade A by releasing other A -degrading enzymes, such as metalloproteases, and gelatinase A [153, 154].”
Background
NAP, a Peptide Derived from the Activity‐Dependent Neuroprotective Protein, Modulates Macrophage Function
Quintana, F. J., Zaltzman, R., Fernández-Montesinos, R., HERRERA, J. L., Gozes, I., Cohen, I. R., & Pozo, D. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1317.069 · Cited by 43 · cited 3×
“These include TNF- [84], IL-6 [85] and IL-12 [85].”
Background
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Astrocyte-Apolipoprotein E Associations in Senile Plaques in Alzheimer Disease and Vascular Lesions
Shao, Y., Gearing, M., & Mirra, S. S. (1997) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199704000-00006 · Cited by 41 · cited 1×
“In an AD patient’s brain, reactive astrocytes are integral components of neuritic plaques [77, 78].”
Background
Identification of soluble CD14 as an endogenous agonist for Toll‐like receptor 2 on human astrocytes by genome‐scale functional screening of glial cell derived proteins
Bsibsi, M., Bajramovic, J. J., van Duijvenvoorden, E., Persoon-Deen, C., Ravid, R., van Noort, J. M., & Vogt, M. H. J. (2007) · Glia · doi:10.1002/glia.20473 · Cited by 40 · cited 6×
“Isolated microglia from postmortem AD and control (non-demented) patients’ brain tissue exhibit pro-inflammatory cytokine expression profiles, in the form of a significantly increased expression of IL-1 , TNF- , IL-6 and IL-12, following an exposure to A peptides.”
Influential
Ccr2 Deficiency Impairs Microglial Accumulation and Accelerates Progression of Alzheimer's Disease
Khoury, J. B. E., Graham, M., Hickman, S. E., Geula, C., Means, T. K., & Luster, A. D. (2007) · Clinical Immunology · doi:10.1016/j.clim.2007.03.030 · Cited by 38
Studies on brain volume, Alzheimer‐related proteins and cytokines in mice with chronic overexpression of IL‐1 receptor antagonist
Oprica, M., Hjorth, E., Spulber, S. D., Popescu, B. O., Ankarcrona, M., Winblad, B. G., & Schultzberg, M. (2007) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2007.00074.x · Cited by 37 · cited 1×
“Pro-inflammatory cytokines, such as interleukin1 (IL-1 / [36, 37], tumour necrosis factor- (TNF- ) [38] and IL-6 [39], may play an important role in AD pathology and lead to an increased production of inducible nitric oxide synthase (iNOS), neuronal stress and further neuronal dysfunction and death [40].”
Background
Identification of an Astrocyte Cell Population from Human Brain that Expresses Perforin, a Cytotoxic Protein Implicated in Immune Defense
Gasque, P., Jones, J. G., Singhrao, S. K., & Morgan, B. P. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.4.451 · Cited by 36
Effects of apoE isoforms on beta-amyloid-induced matrix metalloproteinase-9 in rat astrocytes
Guo, S., Wang, S., Kim, W. J., Lee, S.-R., Frosch, M. P., Bacskai, B. J., Greenberg, S. M., & Lo, E. H. (2006) · Brain Research · doi:10.1016/j.brainres.2006.06.041 · Cited by 34 · cited 1×
“Furthermore, high expression of APOE4 in astrocytes can reduce their response to A deposits [94, 95].”
Background
Novel strategies for Alzheimer's disease treatment
Spencer, B. J., Rockenstein, E. M., Crews, L. A., Marr, R. A., & Masliah, E. (2007) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.7.12.1853 · Cited by 31 · cited 1×
“Adult hippocampal neurogenesis, the process that creates neurons, dramatically decreases with increasing age and it has been proposed that this decline may contribute to age-related memory deficits, such as in AD [168, 169].”
Background
Complement activation in acquired and hereditary amyloid neuropathy
Hafer‐Macko, C. E., Dyck, P. J. B., & Koski, C. L. (2000) · Journal of the Peripheral Nervous System · doi:10.1046/j.1529-8027.2000.00018.x · Cited by 28 · cited 1×
“Complement component 1q (C1q) has been shown to colocalize with most of the amyloid deposits in brains of AD patients [23–25] and triggers a complement cascade, including the formation of the membrane attack complex (MAC), C5b–C9 [26].”
Background
HLA class I, II & III genes in confirmed late-onset Alzheimer's disease
Lehmann, D. J. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00180-9 · Cited by 27
Antibody-mediated immunotherapy for Alzheimer's disease.
Solomon, B. (2007) · PubMed · Cited by 27
Developmental Aspects of Blood–Brain Barrier (BBB) and Rat Brain Endothelial (RBE4) Cells as in vitro Model for Studies on Chlorpyrifos Transport
Yang, J., & Aschner, M. (2003) · NeuroToxicology · doi:10.1016/s0161-813x(03)00025-1 · Cited by 27 · cited 10×
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BackgroundInfluential
Microglial activation by uptake of fDNA via a scavenger receptor
Li, Y., Liu, L., Liu, D., Woodward, S., Barger, S. W., Mrak, R. E., & Griffin, W. S. T. (2003) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2003.10.043 · Cited by 24 · cited 2×
“An accumulation of damaged neuronal DNA fragments can be potent promoters of microglial activation in AD [51].”
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Very early‐onset familial Alzheimer's disease: a novel presenilin 1 mutation
Goldman, J. S., Reed, B., Gearhart, R., Kramer, J. H., & Miller, B. L. (2002) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.657 · Cited by 24 · cited 1×
“Most cases of AD are sporadic, while less than 5% of cases are early onset familial Alzheimer’s disease (EOFAD; age at onset < 65 years) with an autosomal dominant pattern of inheritance [4].”
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The influence of the peptide NAP on Mac-1-deficient mice following closed head injury
Zaltzman, R., Alexandrovich, A. G., Trembovler, V., Shohami, E., & Gozes, I. (2005) · Peptides · doi:10.1016/j.peptides.2005.03.014 · Cited by 22 · cited 1×
“Structure-activity studies identified a short peptide sequence in ADNP, known as a neuronal microtubule-interacting agent (NAP; amino acid sequence NAPVSIPQ), which mimics the neuroprotective activity of the parent protein and crosses the BBB after systemic or intranasal administration and can support the integrity of…”
Background
Treating brain swelling
Paczynski, R. P., & Diringer, M. N. (1996) · Neurology · doi:10.1212/wnl.46.4.1186 · Cited by 13
AD neuropathology
Jellinger, K. A., & Bancher, C. (1996) · Neurology · doi:10.1212/wnl.46.4.1186-b · Cited by 12
Beta-amyloid-based immunotherapy as a treatment of Alzheimer's disease
Solomon, B. (2007) · Drugs of today · doi:10.1358/dot.2007.43.5.1062670 · Cited by 12
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Turner, M. D., Nedjai, B., Hurst, T. P., & Pennington, D. J. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.05.014 · Cited by 2,289
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Authors: Farfara, D., Lifshitz, V., & Frenkel, D.
Affiliations: Tel Aviv University (IL)
Corresponding author: Frenkel, D.
ORCID: Farfara, D.
Frenkel, D.
Venue: Journal of Cellular and Molecular Medicine
Publisher: Wiley
Published: 2008-05-21
Volume: 12
Issue: 3
Pages: 762-780
ISSN: 1582-1838 (ISSN-L)
1582-4934
DOI: 10.1111/j.1582-4934.2008.00314.x
PMC: PMC4401126
OpenAlex: W2022388884
Cited by: 216
References: 202
Citations by year: 2026: 3 · 2025: 7 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 10 · 2020: 13 · 2019: 5 · 2018: 7 · 2017: 9 · 2016: 7 · 2015: 8 · 2014: 15 · 2013: 15 · 2012: 20
FWCI: 2.12
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Cellular and Molecular Medicine (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: Alzheimer's disease, glial cells, microglia, astrocytes, neuroinflammation, innate immune response, amyloid-beta, neurofibrillary tangles, amyloid plaques, complement system, cytokines and chemokines, neuroprotection, neurotoxicity, neurodegeneration, anti-inflammatory therapy
MeSH terms: Alzheimer Disease, Amyloid, Animals, Astrocytes, Brain, Disease Models, Animal, Humans, Models, Neurological, Synaptic Transmission, Synapses, T-Lymphocytes, Amyloid beta-Peptides, Microglia, Endothelial Cells, Plaque, Amyloid

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Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease

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