Cited by 1,287Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsTryptophan and brain disorders

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The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases

MCGEER, P, MCGEER, E·1995·Brain Research Reviews

DOI 10.1016/0165-0173(95)00011-9

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Abstract

Cultured brain cells are capable of generating many molecules associated with inflammatory and immune functions. They constitute the endogenous immune response system of brain. They include complement proteins and their regulators, inflammatory cytokines, acute phase reactants and many proteases and protease inhibitors. Most of the proteins are made by microglia and astrocytes, but even neurons are producers. Many appear in association with Alzheimer disease lesions, indicating a state of chronic inflammation in Alzheimer disease brain. Such a state can apparently exist without stimulation by peripheral inflammatory mediators or the peripheral immune system. A strong inflammatory response may be autotoxic to neurons, exacerbating the fundamental pathology in Alzheimer disease and perhaps other neurological disorders. Autotoxic processes may contribute to cellular death in chronic inflammatory diseases affecting other parts of the body, suggesting the general therapeutic value of anti-inflammatory agents. With respect to Alzheimer disease, multiple epidemiological studies indicate that patients taking anti-inflammatory drugs or suffering from conditions in which such drugs are routinely used, have a decreased risk of developing Alzheimer disease. In one very preliminary clinical trial, the anti-inflammatory drug indomethacin arrested progress of the disease. New agents directed against the inflammatory processes revealed in studies of Alzheimer disease lesions may have broad therapeutic applications.

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Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051
Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue.
McCarthy, K. D., & de Vellis, J. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.85.3.890 · Cited by 3,845
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668
Secretory products of macrophages.
Nathan, C. F. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112815 · Cited by 2,615
Candidate gene for the chromosome 1 familial Alzheimer’s disease locus
Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, W. H., Yu, C.-E., Jondro, P. D., Schmidt, S. D., Wang, K., et al. (1995) · Science · doi:10.1126/science.7638622 · Cited by 2,577
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
Interleukin-8 as a macrophage-derived mediator of angiogenesis
Koch, A. E., Polverini, P. J., Kunkel, S. L., Harlow, L. A., DiPietro, L. A., Elner, V. M., Elner, S. G., & Strieter, R. M. (1992) · Science · doi:10.1126/science.1281554 · Cited by 2,135
Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease.
Griffin, W. S., Stanley, L. C., Ling, C., White, L., MacLeod, V, Perrot, L. J., White, C. L., & Araoz, C. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.19.7611 · Cited by 1,777
Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.
Schmechel, D. E., Saunders, A. M., Strittmatter, W. J., Crain, B. J., Hulette, C. M., Joo, S. H., Pericak-Vance, M. A., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9649 · Cited by 1,525

Show all 319 references

Research works printed but not linked: 4

Del Rio Hortega, 1919, El ‘tercer elemento’ de los centros nerviosos. Poder fagocitario y movilidad de la microglia, Bol. Soc. Esp. Biol. Ano., ix, 154
Raine, 1990, Homing to central nervous system vasculature by antigen-specific lymphocytes, Lab. Invest., 63, 476
Shen, 1995, Expression of membrane attack complex contributes to the increased β-amyloid protein induced neuronal cell death by interruption of complement inhibitor CD59, Neurosci. Abstr., 21, 1009
Wisneiwski, 1973, Re-examination of the pathogenesis of the senile plaque, Vol. 2, 2

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Minami, S. S., Min, S.-W., Krabbe, G., Wang, C., Zhou, Y., Asgarov, R., Li, Y., Martens, L. H., Elia, L. P., Ward, M. E., et al. (2014) · Nature Medicine · doi:10.1038/nm.3672 · Cited by 237
Heme oxygenase expression in human central nervous system disorders
Schipper, H. M. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.09.015 · Cited by 237
Hypermetabolism in ALS: Correlations with Clinical and Paraclinical Parameters
Desport, J., Torny, F., Lacoste, M., Preux, P., & Couratier, P. (2005) · Neurodegenerative Diseases · doi:10.1159/000089626 · Cited by 236
Kaempferol acts through mitogen‐activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells
Park, S. E., Sapkota, K., Kim, S. H., Kim, H., & Kim, S. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01389.x · Cited by 239
“PGE2 is a major eicosanoid found in many inflammatory conditions including CNS inflammatory diseases (McGeer and McGeer, 1995).”
BackgroundInfluential
Inflammatory Aspects of Alzheimer Disease and Other Neurodegenerative Disorders
Schwab, C., & McGeer, P. L. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-13402 · Cited by 235
“Expression of inflammatory mediators has been demonstrated in affected brain regions [45,48].”
Self-citation
Vascular Involvement in Cognitive Decline and Dementia: Epidemiologic Evidence from the Rotterdam Study and the Rotterdam Scan Study
Breteler, M. M. B. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06399.x · Cited by 236
The Role of Sex and Sex Hormones in Neurodegenerative Diseases
Vegeto, E., Villa, A. M., Torre, S. D., Crippa, V., Rusmini, P., Cristofani, R., Galbiati, M., Maggi, A. C., & Poletti, A. (2019) · Endocrine Reviews · doi:10.1210/endrev/bnz005 · Cited by 240
The roles of TNF in brain dysfunction and disease
Clark, I. A., Alleva, L. M., & Vissel, B. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.08.007 · Cited by 239
Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases
Carniglia, L., Ramírez, D., Durand, D., Saba, J., Turati, J., Caruso, C. M., Scimonelli, T. N., & Lasaga, M. (2017) · Mediators of Inflammation · doi:10.1155/2017/5048616 · Cited by 239
Phosphodiesterase type 4 isozymes expression in human brain examined by in situ hybridization histochemistry and [3H]rolipram binding autoradiography
Pérez-Torres, S., Miró, X., Palacios, J. M., Cortés, R., Puigdomènech, P., & Mengod, G. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00097-1 · Cited by 231
Immune reactive cells in senile plaques and cognitive decline in Alzheimer’s disease
Vehmas, A. K., Kawas, C. H., Stewart, W. F., & Troncoso, J. C. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00090-8 · Cited by 230
Amyloid-beta induces chemokine secretion and monocyte migration across a human blood--brain barrier model.
Fiala, M., Zhang, L., Gan, X.-H., Sherry, B. A., Taub, D. D., Graves, M. C., Hama, S., Way, D., Weinand, M. E., Witte, M. H., et al. (1998) · PubMed Central · Cited by 229
Activation of microglial NADPH oxidase is synergistic with glial iNOS expression in inducing neuronal death: a dual-key mechanism of inflammatory neurodegeneration
Mander, P. K., & Brown, G. C. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-20 · Cited by 229
“Thus inflammation may contribute to many CNS pathologies including Alzheimer's, Parkinson's and motor neuron diseases, multiple sclerosis, meningitis, AIDS dementia, strokes, trauma and normal brain ageing [6,7].”
Berry Fruit Supplementation and the Aging Brain
Shukitt‐Hale, B., Lau, F. C., & Joseph, J. A. (2008) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf072505f · Cited by 218
Enhancement of immunoreactivity for NF-κB in the hippocampal formation and cerebral cortex of Alzheimer's disease
Terai, K., Matsuo, A., & McGeer, P. L. (1996) · Brain Research · doi:10.1016/0006-8993(96)00310-1 · Cited by 215
Self-citation
Complement in the pathogenesis of Alzheimer’s disease
Morgan, B. P. (2018) · Seminars in Immunopathology · doi:10.1007/s00281-017-0662-9 · Cited by 194
Effect of hydroxychloroquine on progression of dementia in early Alzheimer's disease: an 18-month randomised, double-blind, placebo-controlled study
van Gool, W. A., Weinstein, H. C., Scheltens, P., & Walstra, G. J. M. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05623-9 · Cited by 210
Amyloid β-protein toxicity and oxidative stress in Alzheimer's disease
Behl, C. (1997) · Cell and Tissue Research · doi:10.1007/s004410050955 · Cited by 212
“For a review of this subject, reference should be made to more specialized original reports and reviews (Rogers et al. 1992; McGeer and McGeer 1995; Finch and Marchalonis 1996; London et al. 1996).”
Background
Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice
Sinz, E. H., Kochanek, P. M., Dixon, C. E., Clark, R. S. B., Carcillo, J. A., Schiding, J. K., Chen, M., Wisniewski, S. R., Carlos, T. M., Williams, D., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6670 · Cited by 211
Dietary Flavonoids as Potential Neuroprotectants
Youdim, K. A., Spencer, J. P. E., Schroeter, H., & Rice-Evans, C. A. (2002) · Biological Chemistry · doi:10.1515/bc.2002.052 · Cited by 210
“Inflammation has also been discussed as an important contributor to neuronal damage in neurodegenerative disorders (McGeer and McGeer, 1996, 1998) and is known to involve the generation of both ROS and RNS. Initial toxic insults may promote neuronal damage resulting in activation of microglial…”
Human neuromelanin induces neuroinflammation and neurodegeneration in the rat substantia nigra: implications for Parkinson's disease
Zecca, L., Wilms, H., Geick, S., Claasen, J.-H., Brandenburg, L.-O., Holzknecht, C., Panizza, M. L., Zucca, F. A., Deuschl, G., Sievers, J., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0361-7 · Cited by 205
“... protective functions, by, for example, supplying glial-derived neurotrophic factor (GDNF), interferons and tumor necrosis factor (TNF-), they may participate in an ongoing cell death following the initial toxic insult by releasing various kinds of noxious factors such as cytokines (i.e., TNF-, IL-1, IL-6) or proin…”
Cytokines, “depression due to a general medical condition”, and antidepressant drugs
Yirmiya, R., Weidenfeld, J., Pollak, Y., Morag, M., Morag, A., Avitsur, R., Barak, O., Reichenberg, A., Cohen, E., Shavit, Y., et al. (1999) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-585-37970-8_16 · Cited by 208
Green tea polyphenols and their potential role in health and disease
Afzal, M., Safer, A.-M., & Menon, M. (2015) · Inflammopharmacology · doi:10.1007/s10787-015-0236-1 · Cited by 215
Aβ-Induced Inflammatory Processes in Microglia Cells of APP23 Transgenic Mice
Bornemann, K. D., Wiederhold, K., Pauli, C., Ermini, F., Stalder, M., Schnell, L., Sommer, B., Jucker, M., & Staufenbiel, M. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63945-4 · Cited by 206
“In particular, microglia cells are considered to play a role in chronic inflammation and possibly neurodegeneration in AD brains.(4,33) In a recent study we have described an APP transgenic mouse line, APP23, and demonstrated abundant microglia reactivity in the vicinity of compact amyloid plaques in the brains of the…”
Background
Dextromethorphan Protects Dopaminergic Neurons against Inflammation-Mediated Degeneration through Inhibition of Microglial Activation
Liu, Y., Qin, L., Li, G., Zhang, W., An, L., Liu, B., & Hong, J. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.043166 · Cited by 205
“…activation of microglia and astroglia, has been closely associated with the pathogenesis of PD, as well as with several other degenerative neurological disorders, including Alzheimer’s disease (McGeer et al., 1988; McGeer and McGeer, 1995; Dickson et al., 1993; Giulian 1999; Liu and Hong, 2003).”
Background
Amyloid β and Amylin Fibrils Induce Increases in Proinflammatory Cytokine and Chemokine Production by THP‐1 Cells and Murine Microglia
Yates, S. L., Burgess, L. H., Kocsis‐Angle, J., Antal, J. M., Dority, M. D., Embury, P. B., Piotrkowski, A. M., & Brunden, K. R. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0741017.x · Cited by 202
Minocycline Reduces the Lipopolysaccharide-Induced Inflammatory Reaction, Peroxynitrite-Mediated Nitration of Proteins, Disruption of the Blood–Brain Barrier, and Damage in the Nigral Dopaminergic System
Tomás-Camardiel, M., Rite, I., Herrera, A. J., de Pablos, R. M., Cano, J., Machado, A., & Venero, J. L. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.01.010 · Cited by 203
Copernicus revisited: amyloid beta in Alzheimer's disease
Josepha, J. A. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00211-6 · Cited by 206
Grape Juice, Berries, and Walnuts Affect Brain Aging and Behavior
Joseph, J. A., Shukitt‐Hale, B., & Willis, L. (2009) · Journal of Nutrition · doi:10.3945/jn.109.108266 · Cited by 203
Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease
Al-Ghraiybah, N. F., Wang, J., Alkhalifa, A. E., Roberts, A. B., Raj, R., Yang, E., & Kaddoumi, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810572 · Cited by 217
Emerging roles of pathogens in Alzheimer disease
Miklossy, J. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411002006 · Cited by 206
“Cellular and humoral components of the immune system reactions are both associated with AD (Refs 98, 99, 100, 101, 102).”
Background
PET Imaging of Inflammation Biomarkers
Wu, C., Li, F., Niu, G., & Chen, X. S. (2013) · Theranostics · doi:10.7150/thno.6592 · Cited by 204
“An increasing number of diseases have recently been found to be inflammation related, such as atherosclerosis [145], neurodegenerative disorders [146],”
Background
Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress
Lindqvist, D., Wolkowitz, O. M., Mellon, S., Yehuda, R., Flory, J. D., Henn-Haase, C., Bierer, L. M., Abu-Amara, D., Coy, M., Neylan, T. C., et al. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.06.003 · Cited by 213
“In addition to peripheral synthesis, cytokines can also be produced within the brain, mainly by astrocytes and microglia (McGeer and McGeer, 1995).”
Background
Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factor-α, interleukin-1β, and nitric oxide
Gayle, D. A., Ling, Z., Tong, C. W., Landers, T. M., Lipton, J. W., & Carvey, P. M. (2002) · Developmental Brain Research · doi:10.1016/s0165-3806(01)00315-7 · Cited by 201
Induction of cytokines in glial cells surrounding cortical β‐amyloid plaques in transgenic Tg2576 mice with Alzheimer pathology
Mehlhorn, G., Hollborn, M., & Schliebs, R. (2000) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(00)00012-5 · Cited by 199
Glial heme oxygenase-1 expression in Alzheimer disease and mild cognitive impairment
Schipper, H. M., BENNETT, D., Liberman, A., Bienias, J. L., Schneider, J. A., Kelly, J. W., & Arvanitakis, Z. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.01.016 · Cited by 199
Cyclooxygenase-2 in synaptic signaling
Yang, H., & Chen, C. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208784480144 · Cited by 195
Temporal Accrual of Complement Proteins in Amyloid Plaques in Down's Syndrome with Alzheimer's Disease
Stoltzner, S. E., Grenfell, T. J., Mori, C., Wisniewski, K. E., Wisniewski, T. M., Selkoe, D. J., & Lemere, C. A. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64753-0 · Cited by 187
Inflammation in Parkinsons Diseases and Other Neurodegenerative Diseases: Cause and Therapeutic Implications
Wilms, H., Zecca, L., Rosenstiel, P. C., Sievers, J., Deuschl, G., & Lucius, R. (2007) · Current Pharmaceutical Design · doi:10.2174/138161207780858429 · Cited by 195
“proteolytic enzymes, reactive oxygen intermediates or nitric oxide) microglia may damage CNS cells [11-14] Nitric oxide (NO) is neurotoxic due to inhibition of complex 1 and 2 of the respiratory chain.”
Background

Authors: MCGEER, P., & MCGEER, E.
Affiliations: University of British Columbia (CA)
Corresponding author: MCGEER, P
Venue: Brain Research Reviews
Publisher: Elsevier BV
Published: 1995-09
Volume: 21
Issue: 2
Pages: 195-218
ISSN: 0165-0173 (ISSN-L)
DOI: 10.1016/0165-0173(95)00011-9
OpenAlex: W2090930997
Cited by: 1,287
References: 319
Citations by year: 2026: 5 · 2025: 12 · 2024: 17 · 2023: 14 · 2022: 24 · 2021: 19 · 2020: 16 · 2019: 18 · 2018: 27 · 2017: 29 · 2016: 19 · 2015: 29 · 2014: 46 · 2013: 42 · 2012: 36
FWCI: 5.59
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Brain Research Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: Alzheimer Society of B.C.
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 › Biological Psychiatry › Tryptophan and brain disorders
Keywords: neuroinflammation, Alzheimer's disease, neurodegenerative diseases, microglia, astrocytes, complement system, inflammatory cytokines, acute phase proteins, chronic inflammation, anti-inflammatory therapy, indomethacin, anti-inflammatory agents, neuroprotection
MeSH terms: Alzheimer Disease, Brain, Humans, Inflammation, Nerve Degeneration, Nervous System Diseases

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The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases

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