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
Systemic infections and inflammation affect chronic neurodegeneration
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Singhrao, S. K., Harding, A., Simmons, T. L., Robinson, S. J., Kesavalu, L. N., & Crean, S. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140387 · Cited by 100
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Background
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Background
Impact of age-related neuroglial cell responses on hippocampal deterioration
Ojo, J. O., Rezaie, P., Gabbott, P. L. A., & Stewart, M. G. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00057 · Cited by 83
“These studies have been able to monitor functional classes of genes showing altered expression in cognitively normal aging across the adult lifespan (age 20–99 years), and have reported that ‘‘immune activation is a highly prominent feature of cognitively normal brain aging which additionally primes the brain for neur…”
Background
Systemic infection modifies the neuroinflammatory response in late stage Alzheimer’s disease
Rakić, S., Hung, Y. M. A., Smith, M., So, D., Tayler, H. M., Varney, W., Wild, J., Harris, S., Holmes, C., Love, S., et al. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0592-3 · Cited by 81
Self-citation
Distinct modulation of microglial amyloid β phagocytosis and migration by neuropeptidesi
Fleisher‐Berkovich, S., Filipovich‐Rimon, T., Ben-Shmuel, S., Hülsmann, C., Kummer, M. P., & Heneka, M. T. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-61 · Cited by 82
“Systemic bacterial infection has been reported to aggravate the clinical symptoms of AD patients [41], a phenomenon which may be explained by several mechanisms.”
Background
Impaired peripheral glucose homeostasis and Alzheimer's disease
Wijesekara, N., Gonçalves, R. A., Felice, F. G. D., & Fraser, P. E. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.027 · Cited by 84
GLP-1 receptor agonists show neuroprotective effects in animal models of diabetes
Gault, V. A., & Hölscher, C. (2018) · Peptides · doi:10.1016/j.peptides.2017.11.017 · Cited by 83
Sociodemographic and lifestyle factors associated with the neutrophil-to-lymphocyte ratio
Howard, R., Scheiner, A., Kanetsky, P. A., & Egan, K. M. (2019) · Annals of Epidemiology · doi:10.1016/j.annepidem.2019.07.015 · Cited by 86
Effects of Selenium Supplementation in Patients with Mild Cognitive Impairment or Alzheimer’s Disease: A Systematic Review and Meta-Analysis
Pereira, M. E., Souza, J. V., Galiciolli, M. E. A., Sare, F., Vieira, G. S., Kruk, I. L., & Oliveira, C. S. (2022) · Nutrients · doi:10.3390/nu14153205 · Cited by 80
“Neurodegenerative diseases, such as AD, are characterized by increased oxidative stress and neuroinflammation, which may be due to the accumulation of βamyloid peptides [7,39,40].”
Background
Re-thinking the Etiological Framework of Neurodegeneration
Castillo, X., Castro‐Obregón, S., Gutiérrez-Becker, B., Gutiérrez‐Ospina, G., Karalis, N., Khalil, A. A., López‐Noguerola, J. S., Rodríguez, L. L., Martínez‐Martínez, E., Perez‐Cruz, C., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00728 · Cited by 80
Chronic periodontitis induces microbiota-gut-brain axis disorders and cognitive impairment in mice
Li, X., Zou, X., Yang, X., Peng, F., Yu, D., & Du, J. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113176 · Cited by 83
Immunosenescence of Natural Killer Cells, Inflammation, and Alzheimer’s Disease
Solana, C., Tarazona, R., & Solana, R. (2018) · International Journal of Alzheimer s Disease · doi:10.1155/2018/3128758 · Cited by 79
“Thus, high levels of tumour necrosis factor (TNF)-α in sera was associated with a 4-fold increase in the rate of cognitive decline [33].”
Background
CD74 interacts with APP and suppresses the production of Aβ
Matsuda, S., Matsuda, Y., & D'adamio, L. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-41 · Cited by 79
“Given the anti-amyloidogenic activity of CD74, it is possible that the increased levels of CD74 in AD brains, potentially caused by increased TNFα in AD patients and in transgenic mouse over expressing APP [41-43], could contribute to a negative feedback mechanism of the organism to fend off noxious APP processing up…”
Background
Brain omega-3 polyunsaturated fatty acids modulate microglia cell number and morphology in response to intracerebroventricular amyloid-β 1-40 in mice
Hopperton, K. E., Trépanier, M., Giuliano, V., & Bazinet, R. P. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0721-5 · Cited by 85
“(TNF)-α is associated with cognitive decline [8].”
Systemic infection exacerbates cerebrovascular dysfunction in Alzheimer’s disease
Asby, D. J., Boche, D., Allan, S. M., Love, S., & Miners, J. S. (2021) · Brain · doi:10.1093/brain/awab094 · Cited by 83
“Systemic infection is a risk factor for progression of Alzheimer’s disease(4,5) and systemic infection and cognitive decline in Alzheimer’s disease are associated with raised serum IL-1b(6) and TNF-a.(7) Modelling of acute systemic infection in rodents induces microglial activation and elevated pro-inflammatory cytoki…”
Background
The influence of cannabinoids on generic traits of neurodegeneration
Fagan, S. G., & Campbell, V. A. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12492 · Cited by 78
Bone Marrow Transplantation Confers Modest Benefits in Mouse Models of Huntington's Disease
Kwan, W., Magnusson, A., Chou, A., Adame, A., Carson, M. J., Kohsaka, S., Masliah, E., Möller, T., Ransohoff, R., Tabrizi, S. J., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4846-11.2012 · Cited by 75
“A recent study showed that acute and chronic systemic inflammation, associated with increases in serum TNF- , is associated with an increase in cognitive decline in AD (Holmes et al., 2009), and, based on our results, we would predict similar findings in HD patients.”
Systemic Immune Responses in Alzheimer's Disease: In Vitro Mononuclear Cell Activation and Cytokine Production
Pellicanò, M., Bulati, M., Buffa, S., Barbagallo, M., Di Prima, A., Misiano, G., Picone, P., Di Carlo, M., Nuzzo, D., Candore, G., et al. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-091714 · Cited by 86
Examining the Relationship between Trace Lithium in Drinking Water and the Rising Rates of Age-Adjusted Alzheimer’s Disease Mortality in Texas
Fajardo, V. A., Fajardo, V. A., LeBlanc, P. J., & MacPherson, R. E. K. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170744 · Cited by 78
Correction: A Systematic Analysis of the Peripheral and CNS Effects of Systemic LPS, IL-1Β, TNF-α and IL-6 Challenges in C57BL/6 Mice
Skelly, D. T., Hennessy, E., Dansereau, M.-A., & Cunningham, C. (2013) · PLoS ONE · doi:10.1371/annotation/90c76048-2edd-4315-8404-4d9d8cbd411e · Cited by 77
Self-citation
TREM2 expression in the human brain: a marker of monocyte recruitment?
Fahrenhold, M., Rakić, S., Classey, J. D., Brayne, C., Ince, P. G., Nicoll, J. A. R., Boche, D., & MRC‐CFAS (2017) · Brain Pathology · doi:10.1111/bpa.12564 · Cited by 74
“In clinical studies, the presence of systemic infection and inflammation, with raised peripheral pro-inflammatory cytokines, was associated with a marked increase in the rate of long-term cognitive decline and the neuropsychiatric features typical of sickness behavior in AD patients (14, 15, 18).”
Background
Creutzfeldt-Jakob disease in a man with COVID-19: SARS-CoV-2-accelerated neurodegeneration?
Young, M. J., O’Hare, M., Matiello, M., & Schmahmann, J. D. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.07.007 · Cited by 77
The intestinal microbiome and Alzheimer's disease: A review
Li, Z., Zhu, H., Zhang, L., & Qin, C. (2018) · Animal Models and Experimental Medicine · doi:10.1002/ame2.12033 · Cited by 78
“inflammation are associated with an increase in cognitive decline in AD patients.(44) The classical pro‐inflammatory cytokine tumor necrosis factor α (TNF‐α) is produced by microglia and is an early cellular marker of AD pathology, and has also been shown to induce neuronal cell cycle events.”
Background
How does cytomegalovirus factor into diseases of aging and vaccine responses, and by what mechanisms?
Aiello, A. E., Chiu, Y.-L., & Frasca, D. (2017) · GeroScience · doi:10.1007/s11357-017-9983-9 · Cited by 73
Cognitive decline in heart failure
Alagiakrishnan, K., Mah, D., Ahmed, A., & Ezekowitz, J. A. (2016) · Heart Failure Reviews · doi:10.1007/s10741-016-9568-1 · Cited by 77
Efficacy and mechanism of cGAMP to suppress Alzheimer’s disease by elevating TREM2
Xu, Q., Xu, W., Cheng, H., Yuan, H., & Tan, X. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.07.004 · Cited by 75
Protective effect of antirheumatic drugs on dementia in rheumatoid arthritis patients
Judge, A., Garriga, C., Arden, N., Lovestone, S., Prieto‐Alhambra, D., Cooper, C. C., & Edwards, C. J. (2017) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.10.002 · Cited by 77
“There is also an association between the levels of cytokines important in the pathogenesis of RA, such as tumor necrosis factor-a or interleukin-10, and progression of dementia [8,31,32].”
Background
Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease
Uddin, M. S., Kabir, M. T., Jalouli, M., Rahman, M. A., Jeandet, P., Behl, T., Alexiou, A. T., Albadrani, G. M., Abdel‐Daim, M. M., Perveen, A., et al. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210826130210 · Cited by 76
“The modulation of neurodegenerative disorders via certain immune molecules as reported in preclinical studies as well as the upregulation of inflammatory genes in tissues derived from individuals with CNS diseases, indicate a link between neurodegeneration including AD and inflammation and suggest the early involvemen…”
Background
Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation
Lehner, K., Silverman, H. A., Addorisio, M. E., Roy, A., Al‐Onaizi, M., Levine, Y. A., Olofsson, P. S., Chavan, S. S., Gros, R., Nathanson, N. M., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00585 · Cited by 72
“Intriguingly, increased peripheral TNF and other pro-inflammatory cytokine levels have been found in Alzheimer’s disease (55), and peripheral inflammation has been linked to exacerbation of brain pathogenesis and neurodegeneration, affecting cholinergic neurons (56, 57).”
Background
A peripheral neutrophil-related inflammatory factor predicts a decline in executive function in mild Alzheimer’s disease
Initiative, A. D. N., Bawa, K. K., Krance, S. H., Herrmann, N., Cogo‐Moreira, H., Ouk, M., Yu, D., Wu, C., Black, S. E., Lanctôt, K. L., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01750-3 · Cited by 72
Cholinergic Modulation of the Immune System in Neuroinflammatory Diseases
Reale, M., & Costantini, E. (2021) · Diseases · doi:10.3390/diseases9020029 · Cited by 76
“Increased levels of circulating pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6, and TNF-α, complement and the presence of activated microglia, have been described in patients with AD, and a direct correlation has been established between Aβ-induced neurotoxicity and cytokine production, and between AD progress…”
Background
CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer’s Disease
Initiative, A. D. N., Zhang, D., Li, J., Wu, H., Cui, Y. J., Bi, R., Zhou, H., Wang, H.-Z., Zhang, C., Wang, D., et al. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.232 · Cited by 73
“It is now known that Aβ plaques and local inflammation are central to the pathogenesis of AD (Kamer, 2010; Wyss-Coray, 2006).”
Background
Autoimmune rheumatic diseases increase dementia risk in middle-aged patients: A nationwide cohort study
Lin, T., Chen, W., Sheu, J., Chen, Y., Chen, J., & Chang, C. (2018) · PLoS ONE · doi:10.1371/journal.pone.0186475 · Cited by 73
Quintessential Risk Factors: Their Role in Promoting Cognitive Dysfunction and Alzheimer’s Disease
Daulatzai, M. A. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0854-6 · Cited by 70
The Receptor for Advanced Glycation Endproducts (RAGE) and Mediation of Inflammatory Neurodegeneration
Derk, J., MacLean, M., Juranek, J., & Schmidt, A. M. (2018) · Journal of Alzheimer’s Disease & Parkinsonism · doi:10.4172/2161-0460.1000421 · Cited by 96
“Altogether, these findings underscore a potentially profound link between peripheral and central inflammation, which prompts the question: to what extent might anti-AGE/RAGE therapies provide protective measures for neurodegeneration and AD, given the prominence of cellular stress driven by increased RAGE ligand burde…”
Background
Systemic Inflammation Impairs Attention and Cognitive Flexibility but Not Associative Learning in Aged Rats: Possible Implications for Delirium
Culley, D. J., Snayd, M., Baxter, M. G., Xie, Z., Lee, I. H., Rudolph, J. L., Inouye, S. K., Marcantonio, E. R., & Crosby, G. J. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00107 · Cited by 70
“…hippocampally mediated cognitive tests in intact animals and are elevated in the brain of patients suffering from dementia (Tancredi et al., 2000; Vereker et al., 2000; Barrientos et al., 2006; Neri et al., 2006; Sparkman et al., 2006; Holmes et al., 2009; Nelson et al., 2011; Westin et al., 2012).”
Background
The Immunology of Delirium
Cerejeira, J., Lagarto, L., & Mukaetova‐Ladinska, E. B. (2014) · NeuroImmunoModulation · doi:10.1159/000356526 · Cited by 72
Reelin through the years: From brain development to inflammation
Alexander, A., Herz, J., & Calvier, L. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112669 · Cited by 76
Resveratrol effects on astrocyte function: Relevance to neurodegenerative diseases
Wight, R. D., Tull, C. A., Deel, M. W., Stroope, B. L., Eubanks, A. G., Chavis, J. A., Drew, P. D., & Hensley, L. L. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.08.045 · Cited by 69
“More recent studies suggest a potential link between high serum levels of CRP with the presence and severity of AD [21] and PD [22–24], suggesting a role of CRP in the pathogenesis of neurodegenerative diseases.”
Anesthesia, surgery, illness and Alzheimer's disease
Eckenhoff, R. G., & Laudansky, K. F. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.06.011 · Cited by 68
“In another recent example, serum levels of the proinflammatory cytokines TNFα and IL-6, measured during a variety of infectious episodes, correlated with both the rate and extent of cognitive decline and in older patients over a 6 month period (Holmes et al., 2009, 2011).”
Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging
Frasca, D., & Blomberg, B. B. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01003 · Cited by 66
“org August 2017 | Volume 8 | Article 1003 Aging is characterized by “inflamm-aging” (23), a low-grade chronic inflammation, which is a risk factor for morbidity and mortality of elderly individuals as it is implicated in the pathogenesis of several disabling diseases of the elderly such as type-2 diabetes mellitus (24…”
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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