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Inflammatory Proteins in Plasma Are Associated with Severity of Alzheimer’s Disease
Open accessAbstract
Markers of Alzheimer's disease (AD) are being widely sought with a number of studies suggesting blood measures of inflammatory proteins as putative biomarkers. Here we report findings from a panel of 27 cytokines and related proteins in over 350 subjects with AD, subjects with Mild Cognitive Impairment (MCI) and elderly normal controls where we also have measures of longitudinal change in cognition and baseline neuroimaging measures of atrophy. In this study, we identify five inflammatory proteins associated with evidence of atrophy on MR imaging data particularly in whole brain, ventricular and entorhinal cortex measures. In addition, we observed six analytes that showed significant change (over a period of one year) in people with fast cognitive decline compared to those with intermediate and slow decline. One of these (IL-10) was also associated with brain atrophy in AD. In conclusion, IL-10 was associated with both clinical and imaging evidence of severity of disease and might therefore have potential to act as biomarker of disease progression.
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“While pathways involving mitochondrial dysfunction or inflammation have been linked to rapid progression, these proteomic and physiological associations may be downstream effects of true drivers of progression [9–11].”
From Genetic drivers of progression in Alzheimer’s disease are distinct from disease risk (2026) · cites this paper as [10]
Experimental — accuracy not yet measuredIn the citing paper
“Elevated CCL11 in the plasma and cerebrospinal fluid seen in aging mice and humans are associated with declining neurogenesis, neurodegenerative disease, and cognitive decline and may contribute to driving neovascularisation in AMD via interaction with CCR3 [1, 93, 123].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [93]
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“Elevated CCL11 in the plasma and cerebrospinal fluid seen in aging mice and humans are associated with declining neurogenesis, neurodegenerative disease, and cognitive decline and may contribute to driving neovascularisation in AMD via interaction with CCR3 [1, 93, 123].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [93]
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Cites
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
The Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods
Jack, C. R., Bernstein, M. A., Fox, N. C., Thompson, P., Alexander, G., Harvey, D., Borowski, B., Britson, P. J., L. Whitwell, J., Ward, C., et al. (2008) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.21049 · Cited by 4,347
McGeer, P. L., Schulzer, M., & McGeer, E. G. (1996) · Neurology · doi:10.1212/wnl.47.2.425 · Cited by 1,367
MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287 · cited 1×
“McGeer & Zhao showed IL-10 can be produced by microglia [35,36].”
BackgroundClassification 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
Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease
Itagaki, S., McGeer, P. L., Akiyama, H., Zhu, S., & Selkoe, D. (1989) · Journal of Neuroimmunology · doi:10.1016/0165-5728(89)90115-x · Cited by 940
Frei, K., Malipiero, U., Leist, T. P., Zinkernagel, R. M., Schwab, M. E., & Fontana, A. (1989) · European Journal of Immunology · doi:10.1002/eji.1830190418 · Cited by 690
Perry, V. H. (2004) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2004.01.004 · Cited by 560
Neuroimaging and Early Diagnosis of Alzheimer Disease: A Look to the Future
Petrella, J. R., Coleman, R. E., & Doraiswamy, P. M. (2003) · Radiology · doi:10.1148/radiol.2262011600 · Cited by 427
Blood-Based Protein Biomarkers for Diagnosis of Alzheimer Disease
Doecke, J. D. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.1282 · Cited by 420
Structural magnetic resonance imaging in the practical assessment of dementia: beyond exclusion
Scheltens, P., Fox, N. C., Barkhof, F., & DeCarli, C. S. (2002) · The Lancet Neurology · doi:10.1016/s1474-4422(02)00002-9 · Cited by 410
Inflammation and neurodegenerative diseases
Griffin, W. S. T. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.2.470s · Cited by 351
Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics
Shaw, L. M. J., Korecka, M., Clark, C. M., Lee, V. M. ‐., & Trojanowski, J. Q. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2176 · Cited by 348
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
Inflammatory factors are elevated in brain microvessels in Alzheimer's disease
Grammas, P. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00276-7 · Cited by 298
Smith, A., Jobst, K., Szatmári, M., Jaskowski, A., King, E., Smith, A., Molyneux, A., Esiri, M., Mcdonald, B., & Wald, N. (1992) · The Lancet · doi:10.1016/0140-6736(92)92890-r · Cited by 280
The significance of neuroinflammation in understanding Alzheimer’s disease
Eikelenboom, P., Veerhuis, R., Scheper, W., Rozemüller, A. J. M., van Gool, W. A., & Hoozemans, J. J. M. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-006-0575-6 · Cited by 268
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
Rozemüller, A. J. M., Eikelenboom, P., Stam, F. C., Beyreuther, K. T., & Masters, C. L. (1989) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198911000-00009 · Cited by 243
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
Entry of Blood-Borne Cytokines into the Central Nervous System: Effects on Cognitive Processes
Banks, W. A., Farr, S. A., & Morley, J. E. (2002) · NeuroImmunoModulation · doi:10.1159/000071472 · Cited by 228
Plasma Biomarkers Associated With the Apolipoprotein E Genotype and Alzheimer Disease
Soares, H. D. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.1070 · Cited by 218
AddNeuroMed—The European Collaboration for the Discovery of Novel Biomarkers for Alzheimer's Disease
Lovestone, S., Francis, P. T., Kłoszewska, I., Mecocci, P., Simmons, A., Soininen, H. S., Spenger, C., Tsolaki, M., Vellas, B. J., Wahlund, L., et al. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05064.x · Cited by 211
Self-citationMedial temporal lobe atrophy on MRI in dementia with Lewy bodies
Barber, R., Gholkar, A., Scheltens, P., Ballard, C., McKeith, I. G., & O’Brien, J. T. (1999) · Neurology · doi:10.1212/wnl.52.6.1153 · Cited by 210
Zhao, B., & Schwartz, J. P. (1998) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19980401)52:1 · Cited by 207
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
Role of imaging techniques in the diagnosis of dementia
O'Brien, J. T. (2007) · British Journal of Radiology · doi:10.1259/bjr/33117326 · Cited by 190
Sanchez‐Ramos, J., Song, S., Sava, V. M., Catlow, B. J., Lin, X., Mori, T., Cao, C., & Arendash, G. W. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.05.071 · Cited by 165
Meda, L., Baron, P., Prat, E., Scarpini, E. A., Scarlato, G., Cassatella, M. A., & Rossi, F. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00188-x · Cited by 157
Microglia, amyloid and dementia in Alzheimer disease
Arends, Y. M., Duyckaerts, C., Rozemuller, J. M., Eikelenboom, P., & Hauw, J.-J. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00094-4 · Cited by 139
Haga, S., Ikeda, K., Sato, M., & Ishii, T. (1993) · Brain Research · doi:10.1016/0006-8993(93)91698-r · Cited by 136
Potential Inflammatory biomarkers in Alzheimer's disease
Mrak, R. E., & Griffin, W. S. T. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-8406 · Cited by 135
Simmons, A., Westman, E., Muehlboeck, S., Mecocci, P., Vellas, B. J., Tsolaki, M., Kłoszewska, I., Wahlund, L., Soininen, H. S., Lovestone, S., et al. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2491 · Cited by 134
Self-citationMRI Measures of Alzheimer's Disease and the AddNeuroMed Study
Simmons, A., Westman, E., Muehlboeck, S., Mecocci, P., Vellas, B. J., Tsolaki, M., Kłoszewska, I., Wahlund, L., Soininen, H. S., Lovestone, S., et al. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05063.x · Cited by 128
Self-citationIdentification of a 5-Protein Biomarker Molecular Signature for Predicting Alzheimer's Disease
Ravetti, M. G., & Moscato, P. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003111 · Cited by 120
Characterization of interleukin-1 production by microglia in culture
Yao, J., Keri, J. E., Taffs, R. E., & Colton, C. A. (1992) · Brain Research · doi:10.1016/0006-8993(92)90981-e · Cited by 118
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
Systemic Inflammatory Markers and Risk of Dementia
Dziedzic, T. (2006) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317506289260 · Cited by 86
Laske, C., Stellos, K., Stransky, E., Leyhe, T., & Gawaz, M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1017 · Cited by 60
Proteomics of Alzheimer’s disease: understanding mechanisms and seeking biomarkers
Lovestone, S., Güntert, A., Hye, A., Lynham, S., Thambisetty, M., & Ward, M. A. (2007) · Expert Review of Proteomics · doi:10.1586/14789450.4.2.227 · Cited by 46
Self-citationBiological Markers in Alzheimer's Disease
Bailey, P. (2007) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100005618 · Cited by 43
Blood-Based Protein Biomarkers for Diagnosis and Classification of Neurodegenerative Diseases
Noelker, C., Hampel, H. J., & Dodel, R. C. (2011) · Molecular Diagnosis & Therapy · doi:10.1007/bf03256398 · Cited by 29
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- Soares HD, Potter WZ, Pickering E, Kuhn M, Immermann FW, <etal>et al</etal>.. (2012) Plasma Biomarkers Associated With the Apolipoprotein E Genotype and Alzheimer Disease. Arch Neurol: 1–8. · DOI · Paper page
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Cattaneo, A., Cattane, N., Galluzzi, S., Provasi, S., Lopizzo, N., Festari, C., Ferrari, C., Guerra, U. P., Paghera, B., Muscio, C., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.08.019 · Cited by 1,382
Lai, K. S. P., Liu, C. S., Rau, A., Lanctôt, K. L., Köhler, C. A., Pakosh, M., Carvalho, A. F., & Herrmann, N. (2017) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2017-316201 · Cited by 433
Peripheral and central immune system crosstalk in Alzheimer disease — a research prospectus
Bettcher, B. M., Tansey, M. G., Dorothée, G., & Heneka, M. T. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00549-x · Cited by 427
Parker, A., Romano, S., Ansorge, R., Aboelnour, A., Le Gall, G., Savva, G. M., Pontifex, M. G., Telatin, A., Baker, D., Jones, E., et al. (2022) · Microbiome · doi:10.1186/s40168-022-01243-w · Cited by 368
A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease
Hampel, H., Caraci, F., Cuello, A. C., Caruso, G., Nisticò, R., Corbo, M., Baldacci, F., Toschi, N., Garaci, F., Chiesa, P. A., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00456 · Cited by 360
Metadata
- Authors
- Leung, R., Proitsi, P., Simmons, A., Lunnon, K., Güntert, A., Kronenberg, D., Pritchard, M., Tsolaki, M., Mecocci, P., Kloszewska, I., Vellas, B., Soininen, H., Wahlund, L.-O., & Lovestone, S.
- Affiliations
- King's College London (GB)
- Aristotle University of Thessaloniki (GR)
- University of Perugia (IT)
- Inserm (FR)
- University of Eastern Finland (FI)
- Corresponding author
- Lovestone, Simon
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-06-10
- Volume
- 8
- Issue
- 6
- Pages
- e64971
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3677891
- OpenAlex
- W2086474013
- Cited by
- 160
- References
- 43
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 18 · 2023: 12 · 2022: 13 · 2021: 19 · 2020: 13 · 2019: 9 · 2018: 15 · 2017: 10 · 2016: 6 · 2015: 15 · 2014: 9 · 2013: 2
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (publishedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- South London and Maudsley NHS Foundation Trust
- Wellcome Trust (100140)
- National Institute for Health and Care Research (NF-SI-0512-10053)
- King's College London
- European Commission (FP6-2004-LIFESCIHEALTH-5)
- Medical Research Council
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, inflammatory proteins, cytokines, biomarkers, disease severity, mild cognitive impairment, brain atrophy, entorhinal cortex, ventriculomegaly, IL-10, cognitive decline, disease progression, neuroimaging
- MeSH terms
- Aged, Alzheimer Disease, Atrophy, Brain, Cognition Disorders, Enzyme-Linked Immunosorbent Assay, Female, Humans, Magnetic Resonance Imaging, Male, Prognosis, Severity of Illness Index, Cohort Studies, Biomarkers, Case-Control Studies, Cytokines, Disease Progression, Inflammation Mediators, Functional Neuroimaging
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