Cited by 1,139Dementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments

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Systemic inflammation and disease progression in Alzheimer disease

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Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., Perry, V. H.·2009·Neurology

DOI 10.1212/wnl.0b013e3181b6bb95PMC PMC2848584

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Abstract

BACKGROUND: Acute and chronic systemic inflammation are characterized by the systemic production of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) that plays a role in immune to brain communication. Previous preclinical research shows that acute systemic inflammation contributes to an exacerbation of neurodegeneration by activation of primed microglial cells. OBJECTIVE: To determine whether acute episodes of systemic inflammation associated with increased TNF-alpha would be associated with long-term cognitive decline in a prospective cohort study of subjects with Alzheimer disease. METHODS: Three hundred community-dwelling subjects with mild to severe Alzheimer disease were cognitively assessed, and a blood sample was taken for systemic inflammatory markers. Each subject's main caregiver was interviewed to assess the presence of incident systemic inflammatory events. Assessments of both patient and caregiver were repeated at 2, 4, and 6 months. RESULTS: Acute systemic inflammatory events, found in around half of all subjects, were associated with an increase in the serum levels of proinflammatory cytokine TNF-alpha and a 2-fold increase in the rate of cognitive decline over a 6-month period. High baseline levels of TNF-alpha were associated with a 4-fold increase in the rate of cognitive decline. Subjects who had low levels of serum TNF-alpha throughout the study showed no cognitive decline over the 6-month period. CONCLUSIONS: Both acute and chronic systemic inflammation, associated with increases in serum tumor necrosis factor alpha, is associated with an increase in cognitive decline in Alzheimer disease.

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McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
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Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589
Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association
Pearson, T. A., Mensah, G. A., Alexander, R. W., Anderson, J. L., Cannon, R. O., Criqui, M., Fadl, Y. Y., Fortmann, S. P., Hong, Y., Myers, G. L., et al. (2003) · Circulation · doi:10.1161/01.cir.0000052939.59093.45 · Cited by 6,401
Clarifying Confusion: The Confusion Assessment Method: A New Method for Detection of Delirium
Inouye, S. K., van Dyck, C. H., Alessi, C. A., Balkin, S., Siegal, A. P., & Horwitz, R. I. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-113-12-941 · Cited by 5,250
A new rating scale for Alzheimer's disease
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.11.1356 · Cited by 4,175
MARKERS OF INFLAMMATION AND CARDIOVASCULAR DISEASE: APPLICATION TO CLINICAL AND PUBLIC HEALTH PRACTICE: A STATEMENT FOR HEALTHCARE PROFESSIONALS FROM THE CENTERS FOR DISEASE CONTROL AND PREVENTION AND THE AMERICAN HEART ASSOCIATION
PearsonT, A., MensahG, A., & AlexanderR, W. (2003) · Journal of Cardiopulmonary Rehabilitation · doi:10.1097/00008483-200305000-00016 · Cited by 2,937
Control of Synaptic Strength by Glial TNFα
Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., Beattie, M. S., & Malenka, R. C. (2002) · Science · doi:10.1126/science.1067859 · Cited by 1,344
Advances in Male Contraception
Page, S. T., Amory, J. K., & Bremner, W. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0041 · Cited by 1,138
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
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Background
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Background
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Gavriel, Y., Rabinovich-Nikitin, I., Ezra, A., Barbiro, B., & Solomon, B. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200506 · Cited by 27
Accelerated accumulation of fibrinogen peptide chains with Aβ deposition in Alzheimer’s disease (AD) mice and human AD brains
Bian, Z., Yamashita, T., Shi, X., Feng, T., Yu, H., Hu, X. F., Hu, X., Bian, Y., Sun, H., Tadokoro, K., et al. (2021) · Brain Research · doi:10.1016/j.brainres.2021.147569 · Cited by 25
Risk of Dementia and Structural Brain Changes Following Nonneurological Infections During 9-Year Follow-Up*
van Ton, A. M. P., Leijsen, E. M. C. M.-V., Bergkamp, M. I., Bronkhorst, E. M., Pickkers, P., de Leeuw, F., Tuladhar, A. M., & Abdo, W. F. (2021) · Critical Care Medicine · doi:10.1097/ccm.0000000000005313 · Cited by 26
“Ear nose throat/upper airway 37 (12) 193 (7)”
Cochlear Inflammaging in Relation to Ion Channels and Mitochondrial Functions
Bazard, P., Pineros, J., Frisina, R. D., Bauer, M. A., Acosta, A. A., Paganella, L. R., Borakiewicz, D., Thivierge, M., Mannering, F. L., Zhu, X., et al. (2021) · Cells · doi:10.3390/cells10102761 · Cited by 27
Sustained peripheral immune hyper-reactivity (SPIHR): an enduring biomarker of altered inflammatory responses in adult rats after perinatal brain injury
Kitase, Y., Chin, E. M., Ramachandra, S., Burkhardt, C., Madurai, N. K., Lenz, C., Hoon, A. H., Robinson, S., & Jantzie, L. L. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02291-z · Cited by 24
Susceptibility to acute cognitive dysfunction in aged mice is underpinned by reduced white matter integrity and microgliosis
Healy, D., Murray, C., McAdams, C., Power, R. W., Hollier, P.-L., Lambe, J., Tortorelli, L. S., López-Rodríguez, A. B., & Cunningham, C. M. (2024) · Communications Biology · doi:10.1038/s42003-023-05662-9 · Cited by 24
Self-citation
The Presence and Origin of Autoantibodies Against α4 and α7 Nicotinic Acetylcholine Receptors in the Human Blood: Possible Relevance to Alzheimer's Pathology
Koval, L., Lykhmus, O., Kalashnyk, O., Bachinskaya, N. Y., Kravtsova, G., Soldatkina, M. A., Zouridakis, M., Stergiou, C., Tzartos, S. J., Tsetlin, V. I., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101845 · Cited by 24
Individual Cytokines Modulate the Neurological Symptoms ofATMDeficiency in a Region Specific Manner
Hui, C. W., & Herrup, K. (2015) · eNeuro · doi:10.1523/eneuro.0032-15.2015 · Cited by 24
“Preconditioning and short-term treatment of LPS have been shown to offer neuroprotection against ischemic hypoxia and brain injuries in rodents (Rosenzweig et al., 2004; Lin et al., 2009; Chen et al., 2012).”
Alzheimer's disease biomarkers in animal models: closing the translational gap.
Sabbagh, J. J., Kinney, J. W., & Cummings, J. L. (2013) · Europe PMC (PubMed Central) · Cited by 24
Mitoxantrone repression of astrocyte activation: Relevance to multiple sclerosis
Burns, S. A., ARCHER, R. L., Chavis, J. A., Tull, C. A., Hensley, L. L., & Drew, P. D. (2012) · Brain Research · doi:10.1016/j.brainres.2012.07.054 · Cited by 24
Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer’s disease
Huang, C., Hsu, S., Tsai, S., Chen, N.-C., Liu, M., Lee, C., Huang, S., Chang, W.-N., Chang, Y., Tsai, W., et al. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0791-z · Cited by 23
“However, it is generally accepted that inflammatory cascades [2] together with neurofibrillary tangles [3] and degenerative neuroimaging biomarkers [4] are more strongly associated with cognitive declines in patients with AD.”
A new Alzheimer's disease cell model using B cells to induce beta amyloid plaque formation and increase TNF alpha expression
Dezfulian, M. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2018.04.012 · Cited by 24
Melatonin-sulforaphane hybrid ITH12674 attenuates glial response in vivo by blocking LPS binding to MD2 and receptor oligomerization
Michalska, P., Buendía, I., Duarte, P., Fernández‐Mendívil, C., Negredo, P., Cuadrado, A., López, M. G., & Leon, R. M. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104597 · Cited by 25
Neurocognitive outcomes after aneurysmal subarachnoid hemorrhage: Identifying inflammatory biomarkers
Watson, E., Ding, D., Khattar, N. K., Everhart, D. E., & James, R. F. (2018) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2018.06.021 · Cited by 23
Gut Microbiota as a Hidden Player in the Pathogenesis of Alzheimer’s Disease
Choi, H., Lee, D., & Mook‐Jung, I. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215235 · Cited by 24
The neutrophil to lymphocyte ratio associates with markers of Alzheimer’s disease pathology in cognitively unimpaired elderly people
Jacobs, T., Jacobson, S. R., Fortea, J., Berger, J. S., Vedvyas, A., Marsh, K., He, T., Gutiérrez‐Jiménez, E., Fillmore, N. R., Gonzalez, M., et al. (2024) · Immunity & Ageing · doi:10.1186/s12979-024-00435-2 · Cited by 27
“Alterations in the levels of peripheral cytokines involved in the innate and adaptive immune response have also been reported in AD patients, and some studies have even linked cytokine levels with the rate of cognitive decline in AD, including TNF-α, IFN-γ, and IL-10 [16–18].”
Background
Neurosyphilis Increases Human Immunodeficiency Virus (HIV)-associated Central Nervous System Inflammation but Does Not Explain Cognitive Impairment in HIV-infected Individuals With Syphilis
Ho, E. L., Maxwell, C. L., Dunaway, S. B., Sahi, S. K., Tantalo, L. C., Lukehart, S. A., & Marra, C. M. (2017) · Clinical Infectious Diseases · doi:10.1093/cid/cix473 · Cited by 25
Decreased neurite density within frontostriatal networks is associated with executive dysfunction in temporal lobe epilepsy
Reyes, A., Uttarwar, V. S., Chang, Y. A., Balachandra, A. R., Pung, C. J., Hagler, D. J., Paul, B. M., & McDonald, C. R. (2017) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2017.09.012 · Cited by 25
Inverse Relationship Between Alzheimer’s Disease and Cancer: How Immune Checkpoints Might Explain the Mechanisms Underlying Age-Related Diseases
Rogers, N. K., Romero, C., SanMartín, C. D., Ponce, D. P., Salech, F., López, M. N., Gleisner, M. A., Tempio, F., & Behrens, M. I. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190839 · Cited by 23
Anti-inflammatory activity of ayahuasca: therapeutical implications in neurological and psychiatric diseases
da Silva, M. G., Daros, G. C., & de Bitencourt, R. M. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.113003 · Cited by 27
Relationship between cerebral atrophy and number of present teeth in elderly individuals with cognitive decline
Egashira, R., Umezaki, Y., Mizutani, S., Obata, T., Yamaguchi, M., Tamai, K., Yoshida, M., Makino, M., & Naito, T. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.111189 · Cited by 22
Warm, Sweetened Milk at the Twilight of Immunity - Alzheimer’s Disease - Inflammaging, Insulin Resistance, M. paratuberculosis and Immunosenescence
Dow, C. T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.714179 · Cited by 22
“at the Twilight of Immunity - Alzheimer’s Disease - Inflammaging, Insulin Resistance, M. paratuberculosis and Immunosenescence.”
BackgroundInfluential
Decreased levels of cytokines implicate altered immune response in plasma of moderate-stage Alzheimer’s disease patients
Koca, S., Kiris, İ., Şahin, Ş., Çınar, N., Karşıdağ, S., Hanağası, H. A., Yıldız, G. B., & Baykal, A. T. (2022) · Neuroscience Letters · doi:10.1016/j.neulet.2022.136799 · Cited by 23
Novel casein antimicrobial peptides for the inhibition of oral pathogenic bacteria
Qi, S., Zhao, S., Zhang, H., Liu, S., Liu, J., Yang, J. H., Qi, Y., Zhao, Q., Jin, Y., & Wang, F. (2023) · Food Chemistry · doi:10.1016/j.foodchem.2023.136454 · Cited by 23
The influence of TNF inhibitors on dementia incidence in patients with rheumatoid arthritis; an analysis from the BSRBR‐RA
McGuinness, B., Holmes, C., Mirakhur, A., Kearsley‐Fleet, L., Vieira, R., Watson, K. D., BSRBR‐RA Contributors Group, & Hyrich, K. L. (2018) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4793 · Cited by 22
“Inflammation is now thought to have a key role in the pathogenesis of Alzheimer’s disease (AD) and other dementias.(1,2) One recent case‐ control analysis showed patients with rheumatoid arthritis (RA) had an increased risk of AD, but this risk was mitigated by treatment with Etanercept, a TNF inhibitor (TNFi).”
BackgroundSelf-citation
Association of nutrition and immune-endocrine dysfunction with muscle mass and performance in cognitively impaired older adults
Tay, L., Leung, B. P. L., Wee, S. L., Tay, K. S., Ali, N., Chan, M. Y., & Lim, W. S. (2017) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2017.11.008 · Cited by 21
Shared Mechanisms of Blood-Brain Barrier Dysfunction and Neuroinflammation in Coronavirus Disease 2019 and Alzheimer Disease
Mayer, M. G., & Fischer, T. (2025) · American Journal Of Pathology · doi:10.1016/j.ajpath.2025.03.011 · Cited by 22
Incretin Hormones GLP-1 and GIP Normalize Energy Utilization and Reduce Inflammation in the Brain in Alzheimer’s Disease and Parkinson’s Disease: From Repurposed GLP-1 Receptor Agonists to Novel Dual GLP-1/GIP Receptor Agonists as Potential Disease-Modifying Therapies
Hölscher, C. (2025) · CNS Drugs · doi:10.1007/s40263-025-01226-z · Cited by 26
The Effects of Immune System Modulation on Prion Disease Susceptibility and Pathogenesis
Mabbott, N. A., Bradford, B. M., Pal, R., Young, R. A., & Donaldson, D. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197299 · Cited by 22
“with Alzheimer’s disease [246,247], Parkinson’s disease [248] and amyotrophic lateral sclerosis or frontotemporal dementia [249].”
Background
Pathway-specific TNF-mediated metaplasticity in hippocampal area CA1
Singh, A., Sateesh, S., Jones, O. D., & Abraham, W. C. (2022) · Scientific Reports · doi:10.1038/s41598-022-05844-1 · Cited by 21
Immunity impacts cognitive deficits across neurological disorders
Shaw, B. C., Anders, V., Tinkey, R. A., Habean, M. L., Brock, O. D., Frostino, B. J., & Williams, J. L. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15999 · Cited by 27
Phenolic‐enriched fractions from brewers' spent grain possess cellular antioxidant and immunomodulatory effects in cell culture model systems
McCarthy, A. L., O’Callaghan, Y. C., Connolly, A., Piggott, C. O., Fitzgerald, R. J., & O’Brien, N. M. (2013) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.6421 · Cited by 21
Transcriptomics of cortical gray matter thickness decline during normal aging
Kochunov, P., Charlesworth, J., Winkler, A. M., Hong, L. E., Nichols, T. E., Curran, J. E., Sprooten, E., Jahanshad, N., Thompson, P. M., Johnson, M. P., et al. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.05.066 · Cited by 23
“…necessary tomaintain the integrity of cerebral tissue (Sharpless and DePinho, 2007; Shook et al., 2011; van Praag et al., 2005) and with activation of the inflammatory pathways that prime the brain for neurodegenerative cascades (Cribbs et al., 2011; Cunningham et al., 2005; Holmes et al., 2009).”
Background
A single systemic inflammatory insult causes acute motor deficits and accelerates disease progression in a mouse model of human tauopathy
Torvell, M., Hampton, D. W., Connick, P., MacLullich, A. M. J., Cunningham, C. M., & Chandran, S. (2019) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.09.001 · Cited by 21
Self-citation
Brain Arrhythmias Induced by Amyloid Beta and Inflammation: Involvement in Alzheimer’s Disease and Other Inflammation-related Pathologies
Peña‐Ortega, F. (2019) · Current Alzheimer Research · doi:10.2174/1567205017666191213162233 · Cited by 21
Perspectives on the Tertiary Prevention Strategy for Alzheimer's Disease
Bu, X., Jiao, S., Lian, Y., & Wang, Y. (2015) · Current Alzheimer Research · doi:10.2174/1567205013666151215110114 · Cited by 20
“Longitudinal studies show that both acute and chronic inflammation are involved in disease progression [66, 67].”
Background
Long-Term PM2.5 Exposure and Neurological Hospital Admissions in the Northeastern United States
Kioumourtzoglou, M., Wang, Y., Dominici, F., Schwartz, J. D., & Zanobetti, A. (2014) · ISEE Conference Abstracts · doi:10.1289/isee.2014.p1-189 · Cited by 21
Alzheimer's Disease
Mandell, A. M., & Green, R. C. (2011) · Wiley eBooks · doi:10.1002/9781444344110.ch1 · Cited by 22
Elevated lipopolysaccharide binding protein in Alzheimer’s disease patients with APOE3/E3 but not APOE3/E4 genotype
Romo, E. Z., Hong, B. V., Patel, R. Y., Agus, J., Harvey, D. J., Maezawa, I., Jin, L., Lebrilla, C. B., & Zivkovic, A. M. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1408220 · Cited by 22
“Higher circulating LBP indicates increased endotoxin exposure, which can initiate neuroinflammatory processes implicated in AD (34).”
Background

Authors: Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H.
Affiliations: Trinity College Dublin (IE)
ORCID: Holmes, C.
Cunningham, C.
Culliford, D.
Perry, V. H.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2009-09-08
Volume: 73
Issue: 10
Pages: 768-774
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.0b013e3181b6bb95
PMC: PMC2848584
OpenAlex: W2085558085
Semantic Scholar: cbac9326b978c2365dec0a3f265816a795105bb1
Cited by: 1,139
References: 42
Citations by year: 2026: 48 · 2025: 68 · 2024: 85 · 2023: 75 · 2022: 77 · 2021: 87 · 2020: 84 · 2019: 89 · 2018: 71 · 2017: 71 · 2016: 59 · 2015: 67 · 2014: 57 · 2013: 55 · 2012: 58
FWCI: 29.59
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Neurology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
Funders: Wellcome Trust (078300)
National Institute for Health and Care Research
National Institutes of Health (5rc2ag036502-02)
Biotechnology and Biological Sciences Research Council
National Institute on Aging (R01AG012101)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: Alzheimer's disease, systemic inflammation, TNF-α, cognitive decline, disease progression, neuroinflammation, microglial activation, inflammatory cytokines, serum biomarkers
MeSH terms: Acute Disease, Aged, Aged, 80 and over, Alzheimer Disease, Chronic Disease, Cognition Disorders, Female, Follow-Up Studies, Humans, Male, Prospective Studies, Retrospective Studies, Tumor Necrosis Factor-alpha, Cohort Studies, Biomarkers, Disease Progression, Inflammation Mediators

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Systemic inflammation and disease progression in Alzheimer disease

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