CoChat
Sign Up
Cited by 7Neuroinflammation and Neurodegeneration MechanismsStress Responses and CortisolAdipokines, Inflammation, and Metabolic Diseases

Monomeric [CRP] and CRP-Controlled Stress and Pain Hypersensitization as Novel Predictors of Cognitive Disturbance and AD in Chronic Inflammatory Disease

Open access
Slevin, Mark, Tero-Vescan, Amelia·2025·International Journal of Molecular Sciences
DOI 10.3390/ijms262311279PMC PMC12692357
Open this paper in CoChat — free accountOpen PDF

Abstract

Chronic low-grade systemic inflammation is increasingly recognized as a key mediator linking stress, pain sensitivity, and cognitive decline. Central to this process are the acute-phase reactants interleukin-6 (IL-6) and C-reactive protein (CRP), which serve as biomarkers of systemic inflammation while promoting neuroimmune dysregulation. Emerging evidence implicates the IL-6–CRP axis in the amplification of pain perception, central sensitization, and stress hypersensitivity, ultimately promoting neurodegenerative processes such as those observed in Alzheimer’s disease (AD) and vascular dementia. Monomeric CRP (mCRP), a proinflammatory isoform generated under mechanical or oxidative stress, can trigger histone modifications (e.g., H3 citrullination), activate endothelial and immune cells, and exacerbate inflammatory pain pathways. These mechanisms are further modulated by genetic and epigenetic factors, including IL-6/CRP/NR3C1 gene variant expression; promoter methylation; and stress-responsive microRNAs, which intersect with dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, impairing immune resolution and neurocognitive resilience. Psychosocial stressors, such as the burden of caregiving or perfectionistic cognitive patterns, amplify IL-6 and CRP levels, particularly when pain is present, suggesting a synergistic interaction between emotional distress and somatic inflammation. Specifically, elevated CRP is associated with increased pain sensitivity, lower pain thresholds, and cognitive decline even in subclinical populations, providing a feedforward model in which chronic stress and pain potentiate systemic inflammation, disrupt neuroendocrine feedback, and accelerate neurodegenerative pathology. However, in this model, the potentially critical mechanistic and pathological role of mCRP remains to be discovered. This review addresses the missing elements of these overlapping pathways and discusses the therapeutic potential of targeting IL-6–CRP signaling, stress regulation, and epigenetic modifiers as strategies to ameliorate inflammation-driven cognitive decline and enhance stress resistance in chronic disease contexts. We propose that plasma mCRP or more likely the isoform-aware metric, the mCRP/CRP ratio, will provide a biologically anchored, potentially more discriminative approach to vascular-neuroimmune risk and capture the propensity for local effector signaling, likely outperforming hs-CRP or IL-6 alone for risk stratification across neurovascular and stress-sensitized pain phenotypes.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/ijms262311279

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Chronic relational stress is increasingly linked to systemic inflammation.

    “In addition to endocrine disruption, chronic relational stress is increasingly linked to systemic inflammation.”

    From From use to abuse: psychological, neurobiological, and spiritual pathways in relational harm and recovery (2026) · cites this paper as Slevin and Tero-Vescan, 2025

    Section 3 links psychosocial stress to systemic low-grade inflammation and discusses stress from caring for a spouse with dementia, a relational stressor. But the caregiving evidence concerns an association between pain and elevated CRP among caregivers; it does not establish the broader claim about chronic relational stress generally. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Elevated levels of inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) have been observed in individuals exposed to prolonged interpersonal trauma.

    “Elevated levels of inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) have been observed in individuals exposed to prolonged interpersonal trauma (Slevin and Tero-Vescan, 2025).”

    From From use to abuse: psychological, neurobiological, and spiritual pathways in relational harm and recovery (2026) · cites this paper as Slevin and Tero-Vescan, 2025

    The Introduction links higher CRP to civilian women with PTSD, and Section 3 reports elevated CRP and IL-6 in patients with somatic symptom and related disorders. Neither passage establishes that CRP, IL-6, and TNF-α are elevated in people exposed to prolonged interpersonal trauma; Section 3 says adverse childhood experiences, apart from sexual trauma, were not strongly associated with the measured biomarkers. No page numbers were provided in our copy. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Studies have demonstrated associations between intimate partner violence and accelerated telomere shortening.

    “Studies have demonstrated associations between intimate partner violence and accelerated telomere shortening, suggesting that chronic emotional abuse may contribute to premature biological aging (Slevin and Tero-Vescan, 2025; Chan et al., 2023).”

    From From use to abuse: psychological, neurobiological, and spiritual pathways in relational harm and recovery (2026) · cites this paper as Slevin and Tero-Vescan, 2025

    The Introduction discusses inflammation and cognitive function in women with PTSD, and Section 6 discusses chronic stress and dementia risk. Neither passage addresses intimate partner violence or telomere shortening. Searches for those terms, biological aging, and emotional abuse found no passage supporting the attributed association. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Chronic emotional abuse may contribute to premature biological aging.

    “Studies have demonstrated associations between intimate partner violence and accelerated telomere shortening, suggesting that chronic emotional abuse may contribute to premature biological aging (Slevin and Tero-Vescan, 2025; Chan et al., 2023).”

    From From use to abuse: psychological, neurobiological, and spiritual pathways in relational harm and recovery (2026) · cites this paper as Slevin and Tero-Vescan, 2025

    Section 6 discusses chronic stress and cognitive decline, while the Abstract discusses stress-related inflammation. Neither addresses intimate partner violence, emotional abuse, telomere shortening, or premature biological aging; searches for those terms found no supporting passage in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

Cited by 7

Research works printed but not linked: 59

  1. [1]Cooper J. Pastorello Y. Slevin M. A Meta-Analysis Investigating the Relationship between Inflammation in Autoimmune Disease, Elevated CRP, and the Risk of Dementia Front. Immunol. 2023 14 1087571 10.3389/fimmu.2023.1087571 36776896 PMC9912841 · DOI
  2. [2]Zhang Z. Na H. Gan Q. Tao Q. Alekseyev Y. Hu J. Yan Z. Yang J.B. Tian H. Zhu S. Monomeric C-reactive Protein via Endothelial CD31 for Neurovascular Inflammation in an ApoE Genotype-dependent Pattern: A Risk Factor for Alzheimer’s Disease? Aging Cell 2021 20 e13501 10.1111/acel.13501 34687487 PMC8590103 · DOI · Paper page
  3. [3]Koyama A. O’Brien J. Weuve J. Blacker D. Metti A.L. Yaffe K. The Role of Peripheral Inflammatory Markers in Dementia and Alzheimer’s Disease: A Meta-Analysis J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2013 68 433 440 10.1093/gerona/gls187 22982688 PMC3693673 · DOI
  4. [4]Long S. Chen Y. Meng Y. Yang Z. Wei M. Li T. Ni J. Shi J. Tian J. Peripheral High Levels of CRP Predict Progression from Normal Cognition to Dementia: A Systematic Review and Meta-Analysis J. Clin. Neurosci. 2023 107 54 63 10.1016/j.jocn.2022.11.016 36502782 · DOI
  5. [5]Williams A.M. Liu W. Ehrhardt M.J. Mirzaei Salehabadi S. Panoskaltsis-Mortari A. Phillips N.S. Mulrooney D.A. Flerlage J.E. Yasui Y. Srivastava D. Systemic Biological Mechanisms of Neurocognitive Dysfunction in Long-Term Survivors of Childhood Hodgkin Lymphoma Clin. Cancer Res. 2024 30 1822 1832 10.1158/1078-0432.CCR-23-3709 38381440 PMC11062814 · DOI
  6. [6]Yuan L. Huang Y. Cheng Y. Correlation between the Degree of Inflammation and Stress Indicators and Concurrent Cognitive Impairment in Patients with Severe Craniocerebral Injury Actas Esp. Psiquiatr. 2024 52 317 324 10.62641/aep.v52i3.1657 38863039 PMC11194158 · DOI
  7. [7]Otsuka T. Hori H. Yoshida F. Itoh M. Lin M. Niwa M. Ino K. Imai R. Ogawa S. Matsui M. Association of CRP Genetic Variation with Symptomatology, Cognitive Function, and Circulating Proinflammatory Markers in Civilian Women with PTSD J. Affect. Disord. 2021 279 640 649 10.1016/j.jad.2020.10.045 33190115 · DOI
  8. [8]Thomas A. Guo J. Reyes-Dumeyer D. Sanchez D. Scarmeas N. Manly J.J. Brickman A.M. Lantigua R.A. Mayeux R. Gu Y. Inflammatory Biomarkers Profiles and Cognition among Older Adults Sci. Rep. 2025 15 2265 10.1038/s41598-025-86309-z 39824904 PMC11748720 · DOI
  9. [9]Fujita C. Sakurai Y. Yasuda Y. Homma R. Huang C.-L. Fujita M. mCRP as a Biomarker of Adult-Onset Still’s Disease: Quantification of mCRP by ELISA Front. Immunol. 2022 13 938173 10.3389/fimmu.2022.938173 35844576 PMC9284222 · DOI
  10. [10]Williams R.D. Moran J.A. Fryer A.A. Littlejohn J.R. Williams H.M. Greenhough T.J. Shrive A.K. Monomeric C-Reactive Protein in Serum with Markedly Elevated CRP Levels Shares Common Calcium-Dependent Ligand Binding Properties with an in Vitro Dissociated Form of C-Reactive Protein Front. Immunol. 2020 11 115 10.3389/fimmu.2020.00115 32117266 PMC7010908 · DOI
  11. [11]Milaneschi Y. Kappelmann N. Ye Z. Lamers F. Moser S. Jones P.B. Burgess S. Penninx B.W.J.H. Khandaker G.M. Association of inflammation with depression and anxiety: Evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts Mol. Psychiatry 2021 26 7393 7402 10.1038/s41380-021-01188-w 34135474 PMC8873022 · DOI
  12. [12]Beurel E. Toups M. Nemeroff C.B. The Bidirectional Relationship of Depression and Inflammation: Double Trouble Neuron 2020 107 234 256 10.1016/j.neuron.2020.06.002 32553197 PMC7381373 · DOI · Paper page
  13. [13]Irwin M.R. Olmstead R. Carroll J.E. Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation Biol. Psychiatry 2016 80 40 52 10.1016/j.biopsych.2015.05.014 26140821 PMC4666828 · DOI · Paper page
  14. [14]Beiner E. Brenner Miguel S. Friederich H.-C. Tesarz J. PerPAIN Consortium Elevated High Sensitive C-Reactive Protein in Fibromyalgia Front. Psychiatry 2023 14 1237518 10.3389/fpsyt.2023.1237518 38098640 PMC10720424 · DOI
  15. [15]Goodyear B.G. Heidari F. Ingram R.J.M. Cortese F. Sharifi N. Kaplan G.G. Ma C. Panaccione R. Sharkey K.A. Swain M.G. Multimodal Brain MRI of Deep Gray Matter Changes Associated with Inflammatory Bowel Disease Inflamm. Bowel Dis. 2023 29 405 416 10.1093/ibd/izac089 35590449 PMC9977255 · DOI
  16. [16]DeVon H.A. Piano M.R. Rosenfeld A.G. Hoppensteadt D.A. The Association of Pain with Protein Inflammatory Biomarkers: A Review of the Literature Nurs. Res. 2014 63 51 62 10.1097/NNR.0000000000000013 24335913 · DOI · Paper page
  17. [17]Graham J.E. Robles T.F. Kiecolt-Glaser J.K. Malarkey W.B. Bissell M.G. Glaser R. Hostility and Pain Are Related to Inflammation in Older Adults Brain Behav. Immun. 2006 20 389 400 10.1016/j.bbi.2005.11.002 16376518 · DOI
  18. [18]Van Den Berg R. Jongbloed E.M. De Schepper E.I.T. Bierma-Zeinstra S.M.A. Koes B.W. Luijsterburg P.A.J. The Association between Pro-Inflammatory Biomarkers and Nonspecific Low Back Pain: A Systematic Review Spine J. 2018 18 2140 2151 10.1016/j.spinee.2018.06.349 29960111 · DOI
  19. [19]Gouin J.-P. Glaser R. Malarkey W.B. Beversdorf D. Kiecolt-Glaser J. Chronic Stress, Daily Stressors, and Circulating Inflammatory Markers Health Psychol. 2012 31 264 268 10.1037/a0025536 21928900 PMC3253267 · DOI · Paper page
  20. [20]Dainese P. Mahieu H. De Mits S. Wittoek R. Stautemas J. Calders P. Associations between Markers of Inflammation and Altered Pain Perception Mechanisms in People with Knee Osteoarthritis: A Systematic Review RMD Open 2023 9 e002945 10.1136/rmdopen-2022-002945 37225282 PMC10231007 · DOI
  21. [21]Shakouri S.K. Dolatkhah N. Omidbakhsh S. Pishgahi A. Hashemian M. Serum Inflammatory and Oxidative Stress Biomarkers Levels Are Associated with Pain Intensity, Pressure Pain Threshold and Quality of Life in Myofascial Pain Syndrome BMC Res. Notes 2020 13 510 10.1186/s13104-020-05352-3 33160410 PMC7648320 · DOI
  22. [22]Schistad E.I. Stubhaug A. Furberg A.-S. Engdahl B.L. Nielsen C.S. C-Reactive Protein and Cold-Pressor Tolerance in the General Population: The Tromsø Study Pain 2017 158 1280 1288 10.1097/j.pain.0000000000000912 28420008 · DOI
  23. [23]Graham-Engeland J. DeMeo N.N. Jones D.R. Mathur A. Smyth J.M. Sliwinski M.J. McGrady M.E. Lipton R.B. Katz M.J. Engeland C.G. Individuals with Both Higher Recent Negative Affect and Physical Pain Have Higher Levels of C-Reactive Protein Brain Behav. Immun. Health 2022 21 100431 10.1016/j.bbih.2022.100431 35243409 PMC8881375 · DOI
  24. [24]Van Der Feltz-Cornelis C.M. Bakker M. Kaul A. Kuijpers T.W. Von Känel R. Van Eck Van Der Sluijs J.F. IL-6 and hsCRP in Somatic Symptom Disorders and Related Disorders Brain Behav. Immun. Health 2020 9 100176 10.1016/j.bbih.2020.100176 34589907 PMC8474154 · DOI
  25. [25]Molnar D.S. Moore J. O’Leary D.D. MacNeil A.J. Wade T.J. Perfectionistic Cognitions, Interleukin-6, and C-Reactive Protein: A Test of the Perfectionism Diathesis Stress Model Brain Behav. Immun. Health 2021 13 100211 10.1016/j.bbih.2021.100211 34589737 PMC8474573 · DOI
  26. [26]Walsh C.P. Lim A. Marsland A.L. Ferrell R.E. Manuck S.B. Circulating Interleukin-6 Concentration Covaries Inversely with Self-Reported Sleep Duration as a Function of Polymorphic Variation in the Glucocorticoid Receptor Brain Behav. Immun. 2019 78 21 30 10.1016/j.bbi.2019.01.002 30639698 PMC6488397 · DOI
  27. [27]Inova A. Birkenæs V. Quintana D.S. Ormerod M.B.E.G. Ueland T. Ueland T. Djurovic S. Andreassen O. Steen N.E. Aas M. Cortisol and C-Reactive Protein (CRP) Regulation in Severe Mental Disorders Psychoneuroendocrinology 2025 172 107272 10.1016/j.psyneuen.2024.107272 39740359 · DOI
  28. [28]Zeller J. Loseff-Silver J. Khoshmanesh K. Baratchi S. Lai A. Nero T.L. Roy A. Watson A. Dayawansa N. Sharma P. Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation Circ. Res. 2024 135 1033 1047 10.1161/CIRCRESAHA.124.324248 39421928 PMC11542976 · DOI
  29. [29]Molins B. Peña E. Vilahur G. Mendieta C. Slevin M. Badimon L. C-Reactive Protein Isoforms Differ in Their Effects on Thrombus Growth Arterioscler. Thromb. Vasc. Biol. 2008 28 2239 2246 10.1161/ATVBAHA.108.174359 18787187 · DOI
  30. [30]Fishman D. Faulds G. Jeffery R. Mohamed-Ali V. Yudkin J.S. Humphries S. Woo P. The Effect of Novel Polymorphisms in the Interleukin-6 (IL-6) Gene on IL-6 Transcription and Plasma IL-6 Levels, and an Association with Systemic-Onset Juvenile Chronic Arthritis J. Clin. Investig. 1998 102 1369 1376 10.1172/JCI2629 9769329 PMC508984 · DOI · Paper page
  31. [31]Van Rossum E.F.C. Polymorphisms in the Glucocorticoid Receptor Gene and Their Associations with Metabolic Parameters and Body Composition Recent Prog. Horm. Res. 2004 59 333 357 10.1210/rp.59.1.333 14749509 · DOI · Paper page
  32. [32]Menke A. Nitschke F. Hellmuth A. Helmel J. Wurst C. Stonawski S. Blickle M. Weiß C. Weber H. Hommers L. Stress Impairs Response to Antidepressants via HPA Axis and Immune System Activation Brain Behav. Immun. 2021 93 132 140 10.1016/j.bbi.2020.12.033 33422640 · DOI · Paper page
  33. [33]Miller G.E. Chen E. Fok A.K. Walker H. Lim A. Nicholls E.F. Cole S. Kobor M.S. Low Early-Life Social Class Leaves a Biological Residue Manifested by Decreased Glucocorticoid and Increased Proinflammatory Signaling Proc. Natl. Acad. Sci. USA 2009 106 14716 14721 10.1073/pnas.0902971106 19617551 PMC2732821 · DOI · Paper page
  34. [34]Pereira-da-Silva T. Napoleão P. Costa M.C. Gabriel A.F. Selas M. Silva F. Enguita F.J. Cruz Ferreira R. Mota Carmo M. Association between miR-146a and Tumor Necrosis Factor Alpha (TNF-α) in Stable Coronary Artery Disease Medicina 2021 57 575 10.3390/medicina57060575 34199767 PMC8230353 · DOI
  35. [35]Karasu E. Halbgebauer R. Schütte L. Greven J. Bläsius F.M. Zeller J. Winninger O. Braig D. Messerer D.A.C. Berger B. A Conformational Change of C-Reactive Protein Drives Neutrophil Extracellular Trap Formation in Inflammation BMC Biol. 2025 23 4 10.1186/s12915-024-02093-8 39773175 PMC11708171 · DOI
  36. [36]Santabárbara J. Lipnicki D.M. Villagrasa B. Lobo E. Lopez-Anton R. Anxiety and Risk of Dementia: Systematic Review and Meta-Analysis of Prospective Cohort Studies Maturitas 2019 119 14 20 10.1016/j.maturitas.2018.10.014 30502746 · DOI
  37. [37]Pollak T.A. Drndarski S. Stone J.M. David A.S. McGuire P. Abbott N.J. The Blood–Brain Barrier in Psychosis Lancet Psychiatry 2018 5 79 92 10.1016/S2215-0366(17)30293-6 28781208 · DOI
  38. [38]Lizano P. Pong S. Santarriaga S. Bannai D. Karmacharya R. Brain Microvascular Endothelial Cells and Blood-Brain Barrier Dysfunction in Psychotic Disorders Mol. Psychiatry 2023 28 3698 3708 10.1038/s41380-023-02255-0 37730841 · DOI
  39. [39]Yamaguchi T. Shimizu K. Kokubu Y. Nishijima M. Takeda S. Ogura H. Kawabata K. Effect of Heat Stress on Blood-Brain Barrier Integrity in iPS Cell-Derived Microvascular Endothelial Cell Models PLoS ONE 2019 14 e0222113 10.1371/journal.pone.0222113 31483843 PMC6726235 · DOI
  40. [40]Tang Y. Fung E. Xu A. Lan H. C-reactive Protein and Ageing Clin. Exp. Pharmacol. Physiol. 2017 44 9 14 10.1111/1440-1681.12758 28378496 · DOI
  41. [41]You Y.-K. Huang X.-R. Chen H.-Y. Lyu X.-F. Liu H.-F. Lan H.Y. C-Reactive Protein Promotes Diabetic Kidney Disease in Db/Db Mice via the CD32b-Smad3-mTOR Signaling Pathway Sci. Rep. 2016 6 26740 10.1038/srep26740 27221338 PMC4879671 · DOI
  42. [42]Chen X. Wang H. Geng P. Ling B. Ma A. Xu M. Tan D. Serum Claudin-5 levels facilitate the early prediction of severe acute pancreatitis: A prospective observational study Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2024 36 930 936 10.3760/cma.j.cn121430-20240318-00247 39380513 · DOI
  43. [43]Bell T.R. Franz C.E. Thomas K.R. Williams M.E. Eyler L.T. Lerman I. Fennema-Notestine C. Puckett O.K. Dorros S.M. Panizzon M.S. Elevated C-Reactive Protein in Older Men with Chronic Pain: Association with Plasma Amyloid Levels and Hippocampal Volume J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2024 79 glae206 10.1093/gerona/glae206 39169831 PMC11439493 · DOI
  44. [44]Schaefer J.K. Engert V. Valk S.L. Singer T. Puhlmann L.M.C. Mapping Pathways to Neuronal Atrophy in Healthy, Mid-Aged Adults: From Chronic Stress to Systemic Inflammation to Neurodegeneration? Brain Behav. Immun. Health 2024 38 100781 10.1016/j.bbih.2024.100781 38725445 PMC11081785 · DOI
  45. [45]Cao B. Xu Q. Shi Y. Zhao R. Li H. Zheng J. Liu F. Wan Y. Wei B. Pathology of Pain and Its Implications for Therapeutic Interventions Signal Transduct. Target. Ther. 2024 9 155 10.1038/s41392-024-01845-w 38851750 PMC11162504 · DOI
  46. [46]Biggerstaff M. Jhung M.A. Reed C. Fry A.M. Balluz L. Finelli L. Influenza-like Illness, the Time to Seek Healthcare, and Influenza Antiviral Receipt During the 2010–2011 Influenza Season—United States J. Infect. Dis. 2014 210 535 544 10.1093/infdis/jiu224 24731959 PMC4610008 · DOI
  47. [47]Schmidt-Wilcke T. Kairys A. Ichesco E. Fernandez-Sanchez M.L. Barjola P. Heitzeg M. Harris R.E. Clauw D.J. Glass J. Williams D.A. Changes in Clinical Pain in Fibromyalgia Patients Correlate with Changes in Brain Activation in the Cingulate Cortex in a Response Inhibition Task Pain Med. 2014 15 1346 1358 10.1111/pme.12460 24995850 · DOI
  48. [48]Fillingim R. Wallace M. Herbstman D. Ribeiro-Dasilva M. Staud R. Genetic Contributions to Pain: A Review of Findings in Humans Oral Dis. 2008 14 673 682 10.1111/j.1601-0825.2008.01458.x 19193196 PMC2667226 · DOI
  49. [49]Sakamoto T. Kobori A. Murakami A. Microarray-Based Label-Free Detection of RNA Using Bispyrene-Modified 2′-O-Methyl Oligoribonucleotide as Capture and Detection Probe Bioorg. Med. Chem. Lett. 2008 18 2590 2593 10.1016/j.bmcl.2008.03.040 18394885 · DOI
  50. [50]Ayub S. Bachu A.K. Jain L. Parnia S. Bhivandkar S. Ahmed R. Kaur J. Karlapati S. Prasad S. Kochhar H. Non-Opioid Psychiatric Medications for Chronic Pain: Systematic Review and Meta-Analysis Front. Pain Res. 2024 5 1398442 10.3389/fpain.2024.1398442 PMC11499177 39449766 · DOI
  51. [51]Camon A.M. Alonso R. Muñoz F.J. Cardozo C. Bernal-Maurandi J. Albiach L. Agüero D. Marcos M.A. Ambrosioni J. Bodro M. C-Reactive Protein Cut-off for Early Tocilizumab and Dexamethasone Prescription in Hospitalized Patients with COVID-19 Sci. Rep. 2022 12 5250 10.1038/s41598-022-08882-x 35347166 PMC8960074 · DOI
  52. [52]Zeller J. Cheung Tung Shing K.S. Nero T.L. McFadyen J.D. Krippner G. Bogner B. Kreuzaler S. Kiefer J. Horner V.K. Braig D. A Novel Phosphocholine-mimetic Inhibits a Pro-inflammatory Conformational Change in C-reactive Protein EMBO Mol. Med. 2023 15 e16236 10.15252/emmm.202216236 36468184 PMC9832874 · DOI
  53. [53]Fujita C. Sakurai Y. Yasuda Y. Fujita M. Monomeric C-Reactive Protein as a Therapeutic Target in Inflammatory Diseases RMD Open 2025 11 e005379 10.1136/rmdopen-2024-005379 41093630 PMC12530421 · DOI
  54. [54]Nikseresht M. Nikseresht M. A Novel Periodized High-repetition Giant-set Resistance and High-intensity Interval Training Effects on the Metabolic and Pro-inflammatory Parameters in Long-and Short-term Overweight Men Eur. J. Sport Sci. 2024 24 127 138 10.1002/ejsc.12038 · DOI
  55. [55]Hölscher C. Glucagon-like Peptide-1 Class Drugs Show Clear Protective Effects in Parkinson’s and Alzheimer’s Disease Clinical Trials: A Revolution in the Making? Neuropharmacology 2024 253 109952 10.1016/j.neuropharm.2024.109952 38677445 · DOI
  56. [56]Chadwick A. Frazier A. Khan T.W. Young E. Understanding the Psychological, Physiological, and Genetic Factors Affecting Precision Pain Medicine: A Narrative Review J. Pain Res. 2021 14 3145 3161 10.2147/JPR.S320863 34675643 PMC8517910 · DOI
  57. [57]Roveta F. Bonino L. Piella E.M. Rainero I. Rubino E. Neuroinflammatory Biomarkers in Alzheimer’s Disease: From Pathophysiology to Clinical Implications Int. J. Mol. Sci. 2024 25 11941 10.3390/ijms252211941 39596011 PMC11593837 · DOI
  58. [58]Delic S. Miletic Drakulic S. Stepovic M. Milosavljevic J. Kovacevic Dimitrijevic M. Jovanovic K. Marinkovic I. Tepavcevic M. Janicijevic N. Mitrovic A. The Connection Between Oxidative Stress, Mitochondrial Dysfunction, Iron Metabolism and Microglia in Multiple Sclerosis: A Narrative Review NeuroSci 2025 6 23 10.3390/neurosci6010023 40137866 PMC11944927 · DOI
  59. [59]Fuglestad A.J. Bousquet P.A. Køstner A.H. Meltzer S. Kleist B. Ree A.H. Rajab I. Potempa L. Fernandez-Botran R. Kersten C. Circulating Levels of the Proinflammatory Monomeric Isoform of C-Reactive Protein (mCRP) Correlate with Intra-Tumoral mCRP Abundance in Stage II–III Colon Cancer Patients J. Inflamm. Res. 2025 18 7115 7125 10.2147/JIR.S485050 40487285 PMC12145102 · DOI

Authors
Slevin, M., & Tero-Vescan, A.
Affiliations
Universitatea de Medicină, Farmacie, Științe și Tehnologie „George Emil Palade” din Târgu Mureș (RO)
Corresponding author
Slevin, Mark
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2025-11-21
Volume
26
Issue
23
Pages
11279
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms262311279
PMC
PMC12692357
OpenAlex
W4416501890
Cited by
7
References
0
Citations by year
2026: 7
FWCI
0.68
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
monomeric C-reactive protein, C-reactive protein, interleukin-6, chronic systemic inflammation, hyperalgesia, central sensitization, cognitive decline, Alzheimer's disease, vascular dementia, neuroinflammation, hypothalamic-pituitary-adrenal axis, epigenetic regulation, microRNA, caregiver burden, perfectionism, neuroimmune dysregulation, biomarkers
MeSH terms
Alzheimer Disease, Animals, C-Reactive Protein, Chronic Disease, Humans, Inflammation, Pain, Stress, Psychological, Biomarkers, Interleukin-6, Cognitive Dysfunction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review