Review: Systemic inflammation andAlzheimer's disease

Alzheimer's disease: the amyloid cascade hypothesis

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Type 2 diabetes as an inflammatory disease

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Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease

Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326

Cyclooxygenase in biology and disease

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High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal

Lotze, M. T., & Tracey, K. J. (2005) · Nature reviews. Immunology · doi:10.1038/nri1594 · Cited by 2,490

Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease

the European Alzheimer's Disease Initiative Investigators, Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.439 · Cited by 2,234

Biological basis of the behavior of sick animals

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Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412

Suntharalingam, G., Perry, M. R., Ward, S., Brett, S. J., Castello-Cortes, A., Brunner, M. D., & Panoskaltsis, N. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa063842 · Cited by 2,164

Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans

Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087

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

Microglia in neurodegenerative disease

Perry, V. H., Nicoll, J. A. R., & Holmes, C. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.17 · Cited by 1,543

Immunoregulatory Feedback Between Interleukin-1 and Glucocorticoid Hormones

Besedovsky, H., del Rey, A., Sorkin, E., & Dinarello, C. A. (1986) · Science · doi:10.1126/science.3014662 · Cited by 1,519

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

Cytokine-Associated Emotional and Cognitive Disturbances in Humans

Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., & Pollmächer, T. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.5.445 · Cited by 1,365

APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy

Rovelet‐Lecrux, A., Hannequin, D., Raux, G., Meur, N. L., Laquerrière, A., Vital, A., Dumanchin‐Njock, C., Feuillette, S., Brice, A., Vercelletto, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1718 · Cited by 1,284

Systemic inflammation and disease progression in Alzheimer disease

Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b6bb95 · Cited by 1,139

Reversing established sepsis with antagonists of endogenous high-mobility group box 1

Yang, H., Ochani, M., Li, J., Qiang, X., Tanovic, M., Harris, H. E., Susarla, S. M., Ulloa, L., Wang, H., DiRaimo, R., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2434651100 · Cited by 1,126

A Meta-Analysis of Cytokines in Alzheimer's Disease

Swardfager, W., Lanctôt, K., Rothenburg, L., Wong, A., Cappell, J., & Herrmann, N. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.06.012 · Cited by 1,108

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

Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial

Tyring, S., Gottlieb, A., Papp, K., Gordon, K., Leonardi, C., Wang, A., Lalla, D., Woolley, M., Jahreis, A., Zitnik, R., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(05)67763-x · Cited by 1,069

The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide

Soscia, S. J., Kirby, J. E., Washicosky, K. J., Tucker, S. M., Ingelsson, M., Hyman, B., Burton, M. A., Goldstein, L. E., Duong, S., Tanzi, R. E., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009505 · Cited by 1,060

In-vivo measurement of activated microglia in dementia

Cagnin, A., Brooks, D. J., Kennedy, A. M., Gunn, R. N., Myers, R., Turkheimer, F. E., Jones, T., & Banati, R. B. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05625-2 · Cited by 1,054

Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins

Ray, S., Britschgi, M., Herbert, C., Takeda-Uchimura, Y., Boxer, A., Blennow, K., Friedman, L. F., Galasko, D. R., Jutel, M., Karydas, A., et al. (2007) · Nature Medicine · doi:10.1038/nm1653 · Cited by 1,048

Cytokine-induced sickness behaviour: mechanisms and implications

Konsman, J. P., Parnet, P., & Dantzer, R. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)02088-9 · Cited by 999

Clinical trial of indomethacin in Alzheimer's disease

Rogers, J., Kirby, L., Hempelman, S. R., Berry, D. A., McGeer, P. L., Kaszniak, A. W., Zalinski, J., Cofield, M., Mansukhani, L., Willson, P., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1609 · Cited by 991

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 916

Age, Neuropathology, and Dementia

Savva, G. M., Wharton, S. B., Ince, P. G., Forster, G., Matthews, F. E., & Brayne, C. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0806142 · Cited by 900

Blood–brain barrier: Ageing and microvascular disease – systematic review and meta-analysis

Farrall, A. J., & Wardlaw, J. M. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.07.015 · Cited by 882

Cytokine-induced sickness behavior: where do we stand?

Dantzer, R. (2001) · Brain, Behavior, and Immunity · doi:10.1006/brbi.2000.0613 · Cited by 862

Regulation of innate immune responses in the brain

Rivest, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2565 · Cited by 843

Neurobehavioral Effects of Interferon-α in Cancer Patients Phenomenology and Paroxetine Responsiveness of Symptom Dimensions

Capuron, L. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00407-9 · Cited by 797

Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum

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Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation

Lee, J. W., Lee, Y. K., Yuk, D. Y., Choi, D. Y., Ban, S. B., Oh, K. W., & Hong, J. T. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-37 · Cited by 772

Central and Systemic Endotoxin Challenges Exacerbate the Local Inflammatory Response and Increase Neuronal Death during Chronic Neurodegeneration

Cunningham, C., Wilcockson, D. C., Campion, S., Lunnon, K., & Perry, V. H. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2614-05.2005 · Cited by 768

Rates and risk factors for dementia and Alzheimer’s disease: Results from EURODEM pooled analyses

Launer, L. J., Andersen, K., Dewey, M. E., Letenneur, L., Ott, A., Amaducci, L. A., Brayne, C., Copeland, J. R. M., Dartigues, J.-F., Kragh-Sorensen, P., et al. (1999) · Neurology · doi:10.1212/wnl.52.1.78 · Cited by 758

Inflammation Causes Mood Changes Through Alterations in Subgenual Cingulate Activity and Mesolimbic Connectivity

Harrison, N. A., Brydon, L., Walker, C., Gray, M. A., Steptoe, A., & Critchley, H. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.015 · Cited by 756

TLR3: Interferon induction by double-stranded RNA including poly(I:C)☆

MATSUMOTO, M., & Seya, T. (2008) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.11.005 · Cited by 704

Lipopolysaccharide-Induced Inflammation Exacerbates Tau Pathology by a Cyclin-Dependent Kinase 5-Mediated Pathway in a Transgenic Model of Alzheimer's Disease

Kitazawa, M., Oddo, S., Yamasaki, T. R., Green, K. N., & LaFerla, F. M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2868-05.2005 · Cited by 697

Immune activation in brain aging and neurodegeneration: too much or too little?

Lucin, K. M., & Wyss-Coray, T. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.039 · Cited by 679

Cerebral Microglia Recruit Monocytes into the Brain in Response to Tumor Necrosis Factorα Signaling during Peripheral Organ Inflammation

D'Mello, C., Le, T., & Swain, M. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3567-08.2009 · Cited by 675

Blood brain barrier: ageing and microvascular disease-systematic review and meta-analysis

Farrall, A., & Wardlaw, J. M. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2009.02.089 · Cited by 640

Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E

Barger, S. W., & Harmon, A. D. (1997) · Nature · doi:10.1038/42257 · Cited by 622

Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer’s disease

Jones, L., Holmans, P. A., Hamshere, M. L., Harold, D., Moskvina, V., Ivanov, D., Pocklington, A., Abraham, R., Hollingworth, P., Sims, R., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013950 · Cited by 606

When Two Strands Are Better Than One: The Mediators and Modulators of the Cellular Responses to Double-Stranded RNA

Jacobs, B. L., & Langland, J. (1996) · Virology · doi:10.1006/viro.1996.0259 · Cited by 588

Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease.

Cunningham, C., Campion, S., Lunnon, K., Murray, C. L., Woods, J. F. C., Deacon, R. M. J., Rawlins, J. N. P., & Perry, V. H. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.07.024 · Cited by 584

Predictors of cognitive decline and mortality of aged people over a 10‐year period

Tilvis, R. S., Kahonen-Vare, M. H., Jolkkonen, J., Valvanne, J., Pitkala, K. H., & Strandberg, T. E. (2004) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/59.3.m268 · Cited by 578

Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins

Casserly, I., & Topol, E. J. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15900-x · Cited by 560

Elevated circulating tumor necrosis factor levels in Alzheimer's disease

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Microglia, amyloid, and cognition in Alzheimer's disease: An [11C](R)PK11195-PET and [11C]PIB-PET study

Edison, P., Archer, H. A., Gerhard, A., Hinz, R., Pavese, N., Turkheimer, F. E., Hammers, A., Tai, Y. F., Fox, N., Kennedy, A., et al. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.08.001 · Cited by 513

Delirium accelerates cognitive decline in Alzheimer disease

Fong, T. G., Jones, R. N., Shi, P., Marcantonio, E. R., Yap, L., Rudolph, J. L., Yang, F. M., Kiely, D. K., & Inouye, S. K. (2009) · Neurology · doi:10.1212/wnl.0b013e3181a4129a · Cited by 501

Alzheimer's disease: The amyloid cascade hypothesis: An update and reappraisal

Hardy, J. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s317 · Cited by 475

A randomized controlled trial of prednisone in Alzheimer’s disease

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A High Plasma Concentration of TNF- Is Associated With Dementia in Centenarians

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Activation of Vagal Afferents after Intravenous Injection of Interleukin-1β: Role of Endogenous Prostaglandins

Ek, M., Kurosawa, M., Lundeberg, T., & Ericsson, A. B. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-22-09471.1998 · Cited by 452

Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents

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Recombinant mouse gamma interferon induces the priming step in macrophage activation for tumor cell killing.

Pace, J. L., Russell, S. W., Torres, B. A., Johnson, H. M., & Gray, P. W. (1983) · The Journal of Immunology · doi:10.4049/jimmunol.130.5.2011 · Cited by 441

Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe

Feldman, H. H., Doody, R. S., Kivipelto, M., Sparks, D. L., Waters, D. D., Jones, R. W., Schwam, E., Schindler, R., Hey-Hadavi, J., DeMicco, D. A., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181d6476a · Cited by 438

Cytokines and fever

Conti, B. (2004) · Frontiers in bioscience · doi:10.2741/1341 · Cited by 417

Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26‐week randomized, placebo‐controlled, double‐blind trial

Simons, M., Schwärzler, F., Lütjohann, D., von Bergmann, K., Beyreuther, K. T., DICHGANS, J., Wormstall, H., Hartmann, T., & Schulz, J. B. (2002) · Annals of Neurology · doi:10.1002/ana.10292 · Cited by 413

Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis

Kuo, H., Yen, C., Chang, C., Kuo, C.-K., Chen, J.-H., & Sorond, F. A. (2005) · The Lancet Neurology · doi:10.1016/s1474-4422(05)70099-5 · Cited by 409

Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent?

Dantzer, R., Konsman, J.-P., Bluthé, R.-M., & Kelley, K. W. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00220-4 · Cited by 400

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

Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice

Krstic, D., Madhusudan, A., Doehner, J., Vogel, P., Notter, T., Imhof, C., Manalastas, A., Hilfiker, M., Pfister, S., Schwerdel, C., et al. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-151 · Cited by 400

Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid β peptide in APPswe transgenic mice

Sheng, J. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00069-x · Cited by 388

Cognitive Function Over Time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): Results of a Randomized, Controlled Trial of Naproxen and Celecoxib

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A randomized controlled trial of prednisone in Alzheimer’s disease

Koch, H. J., & Szecsey, A. (2000) · Neurology · doi:10.1212/wnl.55.7.1067 · Cited by 381

Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans

Brydon, L., Harrison, N. A., Walker, C., Steptoe, A., & Critchley, H. D. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.12.007 · Cited by 381

Tooth loss, dementia and neuropathology in the Nun Study

Stein, P. S., Desrosiers, M. F., DONEGAN, S. J., Yepes, J. F., & Kryscio, R. J. (2007) · The Journal of the American Dental Association · doi:10.14219/jada.archive.2007.0046 · Cited by 380

Evidence for a Potent Antiinflammatory Effect of Rosiglitazone

Mohanty, P., Aljada, A., Ghanim, H., Hofmeyer, D., Tripathy, D., Syed, T., Al-Haddad, W., Dhindsa, S., & Dandona, P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-032103 · Cited by 378

Coexpression of Microsomal-Type Prostaglandin E Synthase with Cyclooxygenase-2 in Brain Endothelial Cells of Rats during Endotoxin-Induced Fever

Yamagata, K., Matsumura, K., Inoue, W., Shiraki, T., Suzuki, K., Yasuda, S., Sugiura, H., Cao, C., Watanabe, Y., & Kobayashi, S. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-08-02669.2001 · Cited by 372

Neuroprotective role of the innate immune system by microglia

Glezer, I., Simard, A. R., & Rivest, S. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.02.055 · Cited by 371

Microglial activation and amyloid deposition in mild cognitive impairment: A PET study

Okello, A., Edison, P., Archer, H. A., Turkheimer, F. E., Kennedy, J., Bullock, R., Walker, Z., Kennedy, A., Fox, N., Rossor, M., et al. (2009) · Neurology · doi:10.1212/01.wnl.0000338622.27876.0d · Cited by 367

Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer’s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study

Gold, M., Alderton, C., Zvartau-Hind, M., Egginton, S., Saunders, A. M., Irizarry, M., Craft, S., Landreth, G., Linnamägi, Ü., & Sawchak, S. (2010) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000318845 · Cited by 361

Interleukin-1β in Immune Cells of the Abdominal Vagus Nerve: a Link between the Immune and Nervous Systems?

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The Neuropathology of Septic Shock

Sharshar, T., Annane, D., de la Gradmaison, G. L., Brouland, J. P., Hopkinson, N. S., & Gray, F. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00494.x · Cited by 348

Pathway across the blood–brain barrier

Ek, M., Engblom, D., Saha, S., Blomqvist, A. G., Jakobsson, P., & Ericsson‐Dahlstrand, A. (2001) · Nature · doi:10.1038/35068632 · Cited by 347

Neural Origins of Human Sickness in Interoceptive Responses to Inflammation

Harrison, N. A., Brydon, L., Walker, C., Gray, M. A., Steptoe, A., Dolan, R. J., & Critchley, H. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.007 · Cited by 345

A4POE*4-associated Alzheimer's disease risk is modified by α1–antichymotrypsin polymorphism

Kamboh, M. I., Sanghera, D. K., Ferrell, R. E., & DeKosky, S. T. (1995) · Nature Genetics · doi:10.1038/ng0895-486 · Cited by 336

Extended results of the Alzheimer's disease anti‐inflammatory prevention trial

Breitner, J. C. S., Baker, L. D., Montine, T. J., Meinert, C. L., Lyketsos, C. G., Ashe, K. H., Brandt, J., Craft, S., Evans, D. A., Green, R. C., et al. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.12.014 · Cited by 327

Vagal Paraganglia Bind Biotinylated Interleukin-1 Receptor Antagonist: A Possible Mechanism for Immune-to-Brain Communication

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Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1.

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Atorvastatin for the Treatment of Mild to Moderate Alzheimer Disease: Preliminary Results

Sparks, D. L., Sabbagh, M. N., Connor, D. J., Lopez, J., Launer, L. J., Browne, P., Wasser, D., Johnson-Traver, S., Lochhead, J., & Ziolwolski, C. (2005) · Archives of Neurology · doi:10.1001/archneur.62.5.753 · Cited by 319

Anorexia of infection as a mechanism of host defense

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Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease

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Interleukin-6 Facilitates Lipopolysaccharide-Induced Disruption in Working Memory and Expression of Other Proinflammatory Cytokines in Hippocampal Neuronal Cell Layers

Sparkman, N. L., Buchanan, J. B., Heyen, J. R. R., Chen, J., Beverly, J. L., & Johnson, R. W. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3376-06.2006 · Cited by 307

Endotoxin-induced activation of cerebral catecholamine and serotonin metabolism: comparison with interleukin-1.

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The role of TNF and its receptors in Alzheimer's disease

Perry, R. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00291-3 · Cited by 301

Inflammation, A beta deposition, and neurofibrillary tangle formation as correlates of Alzheimer's disease neurodegeneration.

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Systematic interleukin-1 administration stimulates hypothalamic norepinephrine metabolism parallelling the increased plasma corticosterone

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Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology?

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