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ORIGINAL PAPER
Relationship of C-reactive protein and Tau protein serum levels during ischemic stroke
 
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1
Department of Neurology, Medical University of Lublin, Poland
 
2
Department of Clinical Psychology and Neuropsychology, Faculty of Pedagogy and Psychology, Maria Curie-Skłodowska University, Lublin, Poland
 
3
Department of Medical Chemistry, Medical University of Lublin, Poland
 
 
Submission date: 2023-11-29
 
 
Final revision date: 2024-07-14
 
 
Acceptance date: 2024-07-31
 
 
Publication date: 2025-04-18
 
 
Medical Studies 2025;41(2):103-109
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Results of some studies suggest that inflammation which occurs during ischemic stroke (IS) can trigger neurodegenerative damage of brain tissue. This may explain how IS can lead to vascular dementia (VaD) and co-existence of VaD and AD.

Aim of the research:
The aim of our study was to discover whether C-reactive protein (CRP) contributes to the releasing of Tau protein into the blood during IS. This may help explain the mechanism of development of the neurodegenerative processes in stroke patients.

Material and methods:
Clinical status of 54 patients with IS was evaluated on day 1, 3, 5, 10 and 3 months after the onset of the stroke. The volume of ischemic focus was calculated on day 10 using CT with the planimetric method. Serum levels of CRP and Tau protein were evaluated on day 1, 3, 5 and 10 during the acute phase of IS. We divided patients into 3 groups according to the mean levels of CRP on day 5: group 1 with normal range of CRP (0–5 mg/l), group 2 with abnormal but lower range of CRP (5.01–48 mg/l) and group 3 with abnormal and higher range of CRP (> 48.1 mg/l).

Results:
The mean serum level of CRP correlates positively with the mean serum level of Tau protein (rs = 0.41, p < 0.01). Tau protein levels measured on day 10 were significantly different in every group of CRP (p < 0.05).

Conclusions:
The presence and level of Tau protein in serum of patients with IS can be determined by CRP concentration.
REFERENCES (55)
1.
Tracz J, Gorczyca-Głowacka I, Wełnicki M, Kołodziejska E, Rosołowska A, Mamcarz A, Wożakowska-Kapłon B. Ischaemic stroke in women and men – in-hospital prognosis. Medical Studies. 2022; 38: 22-30.
 
2.
Tracz J, Gorczyca-Głowacka I, Wałek P, Rosołowska A, Wożakowska-Kapłon B. Risk factors of ischaemic stroke in patients with atrial fibrillation. Medical Studies. 2023; 39: 8-13.
 
3.
Goerlic PB, Scuteri A, Black SE, Decarli C. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American heart association/American stroke association. Stroke. 2011; 42: 2672-2713.
 
4.
Iadecola C. The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol. 2010; 120: 287-296.
 
5.
Cumming T, Brodtmann A. Can stroke cause neurodegenerative dementia? Int J Stroke. 2011 Oct; 6(5): 416-424.
 
6.
Volanakis JE. Human C-reactive protein: expression, structure, and function. Mol Immunol. 2001 Aug; 38(2-3): 189-197.
 
7.
Kushner I. C-reactive protein – my perspective on its first half century, 1930-1982. Front Immunol. 2023 Mar; 14: 1150103.
 
8.
Blac S, Kusher I, Samols D. C-reactive protein. J Biol Chem. 2004 Nov; 279(47): 48487-48490.
 
9.
Thompson D, Pepys MB, Wood SP. The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure. 1999 Feb; 7(2): 169-177.
 
10.
Nordestgaard BG, Zacho J. Lipids, atherosclerosis and CVD risk: is CRP an innocent bystander? Nutr Metab Cardiovasc Dis. 2009 Oct; 19(8): 521-524.
 
11.
Martinez BK, White CM. The emerging role of inflammation in cardiovascular disease. Ann Pharmacother. 2018 Aug; 52(8): 801-809.
 
12.
Li JJ, Fang CH. C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases. Med Hypotheses. 2004; 62(4): 499-506.
 
13.
Blake GJ, Ridker PM. Novel clinical markers of vascular wall inflammation. Circ Res. 2001 Oct; 89(9): 763-771.
 
14.
Futterman LG, Lemberg L. High-sensitivity C-reactive protein is the most effective prognostic measurement of acute coronary events. Am J Crit Care. 2002 Sep; 11(5): 482-486.
 
15.
Muir KW, Weir CJ, Alwan W. C-reactive protein and outcome after ischemic stroke. Stroke. 1999 May; 30(5): 981-985.
 
16.
Welsh P, Barber M, Langhorne P. Associations of inflammatory and haemostatic biomarkers with poor outcome in acute ischemic stroke. Cerebrovasc Dis. 2009; 27(3): 247-253.
 
17.
Bian J, Guo S, Huang T, Li X, Zhao S, Chu Z, Li Z. CRP as a potential predictor of outcome in acute ischemic stroke. Biomed Rep. 2023 Jan; 18(2): 17.
 
18.
Shantikumar S, Grant PJ, Catto A. Elevated C-reactive protein and long-term mortality after ischemic stroke. Stroke. 2009; 40: 977.
 
19.
Kim KY, Shin KY, Chang KA. Potential biomarkers for post-stroke cognitive impairment: a systematic review and meta-analysis. Int J Mol Sci. 2022 Jan; 23 (2): 602.
 
20.
Yang Y, Zhu L, Zhang B, Gao J, Zhao T, Fang S. Higher levels of C-reactive protein in the acute phase of stroke indicate an increased risk for post-stroke depression: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2022 Mar; 134: 104309.
 
21.
Shen XN, Niu LD, Wang YJ, Cao XP, Liu Q, Tan L, Zhang C, Yu JT. Inflammatory markers in Alzheimer’s disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies. J Neurol Neurosurg Psychiatry. 2019 May; 90: 590-598.
 
22.
Ravaglia G, Forti P, Maioli F. Blood inflammatory markers and risk of dementia: the Conselice Study of Brain Aging. Neurobiol Aging. 2007 Dec; 28(12): 1810-1820.
 
23.
Esposito F, Matthes H, Schad F. Seven COVID-19 patients treated with C-reactive protein (CRP) apheresis. J Clin Med. 2022 Apr; 11(7): 1956.
 
24.
Torzewski J, Brunner P, Ries W, Garlichs CD, Kayser S, Heigl F, Sheriff A. Targeting C-reactive protein by selective apheresis in humans: pros and cons. J Clin Med. 2022 Mar; 11(7): 1771.
 
25.
Tabeshmehr P, Eftekharpour E. Tau; one protein, so many diseases. Biology. 2023 Feb; 12(2): 244.
 
26.
Gendron TF, Petrucelli L. The role of tau in neurodegeneration. Mol Neurodegener. 2009 Mar; 4: 13.
 
27.
Ittner A, Ke YD, Eersel J, Gladbach A, Gotz J, Ittner LM. Brief update on different roles of tau in neurodegeneration. IUBMB Life. 2011 Jul; 63(7): 495-502.
 
28.
Fagan AM, Holtzman DM. Cerebrospinal fluid biomarkers of Alzheimer’s disease. Biomark Med. 2010 Feb; 4(1): 51-63.
 
29.
Jack CR Jr, Knopman DS, Jagust WJ. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010 Jan; 9(1): 119-128.
 
30.
Morris M, Maeda S, Vossel K. The many faces of tau. Neuron. 2011 May; 70(3): 410-426.
 
31.
Bitsch A, Horn C, Kemmling Y. Serum Tau protein level as a marker of axonal damage in acute ischemic stroke. Eur Neurol. 2002; 47: 45-51.
 
32.
Guzel A, Karasalihoglu S, Aylanc T. Validity of serum tau protein levels in pediatric patients with minor head trauma. Am J Emerg Med. 2010 May; 28(4): 399-403.
 
33.
van Harten AC, Kester MI, Visser PJ. Tau and p-tau as CSF biomarkers in dementia: a meta-analysis. Clin Chem Lab Med. 2011 Mar; 49(3): 353-366.
 
34.
Goedert M, Spillantini MG. Propagation of Tau aggregates. Mol Brain. 2017 May; 10(1): 18.
 
35.
Fujii H, Takahashi T, Mukai T, Tanaka S, Hosomi N, Maruyama H, Sakai N, Matsumoto M. Modifications of tau protein after cerebral ischemia and reperfusion in rats are similar to those occurring in Alzheimer’s disease - hyperphosphorylation and cleavage of 4- and 3-repeat tau. J Cereb Blood Flow Metab. 2017; 37: 2441-2457.
 
36.
Wen Y, Yang S, Liu R, Brun-Zinkernagel AM, Koulen P, Simpkins JW. Transient cerebral ischemia induces aberrant neuronal cell cycle re-entry and Alzheimer’s disease-like tauopathy in female rats. J Biol Chem 2004 May; 279(21): 22684-22692.
 
37.
Di Napoli M, Shah IM. Neuroinflammation and cerebrovascular disease in old age: a translational medicine perspective. J Aging Res. 2011; 2011: 857484.
 
38.
Gonzalez-Ortiz F, Turton M, Kac PR, Smirnov D, Premi E, Ghidoni R, Benussi L, Cantoni V, Saraceno C, Rivolta J, Ashton NJ, Borroni B, Galasko D, Harrison P, Zetter- berg H, Blennow K, Karikari TK. Brain-derived tau: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration Brain. 2023 Mar; 146(3): 1152-1165.
 
39.
Bielewicz J, Kurzepa J, Czekajska-Chehab et al. Does serum Tau protein predict the outcome of patients with ischemic stroke? J Mol Neurosci. 2011 Mar; 43(3): 241-245.
 
40.
Mörtberg E, Zetterberg H, Nordmark J, Blennow K, Ca- try C, Decraemer H, Vanmechelen E, Rubertsson S. Plasma tau protein in comatose patients after cardiac arrest treated with therapeutic hypothermia. Acta Anaesthesiol Scand. 2011; d55: 1132-1138.
 
41.
Guo T, Noble W, Hanger DP. Roles of tau protein in health and disease. Acta Neuropathol. 2017 May; 133(5): 665-704.
 
42.
Chen YD, Huang PY, Chiang CS, Huang YS, Tang SC. Generation and role of calpain-cleaved 17-kDa Tau fragment in acute ischemic stroke. Mol Neurobiol. 2021 Nov; 58(11): 5814-5825.
 
43.
Pluta R, Kiś J, Januszewski S, Jabłoński M, Czuczwar SJ. Cross-talk between amyloid, tau protein and free radicals in post-ischemic brain neurodegeneration in the form of Alzheimer’s disease proteinopathy. Antioxidants (Basel). 2022 Jan; 11(1): 146.
 
44.
Irving EA, Nicoll J, Graham DI, Dewar D. Increased tau immunoreactivity in oligodendrocytes following human stroke and head injury. Neurosci Lett. 1996; 213: 189-192.
 
45.
Härtig W, Krueger M, Hofmann S, Preißler H, Märkel M, Frydrychowicz C, Mueller WC, Bechmann I, Michal- ski DJ. Up-regulation of neurofilament light chains is associated with diminished immunoreactivities for MAP2 and tau after ischemic stroke in rodents and in a human case. Chem Neuroanat. 2016 Dec; 78: 140-148.
 
46.
Heshmatollah A, Fani L, Koudstaal PJ, Ghanbari M, Ikram MA, Ikram MK. Plasma -amyloid, total-Tau, and neurofilament light chain levels and the risk of stroke: a prospective population-based study. Neurology. 2022 Apr; 98(17): e1729-e1737.
 
47.
Hjalmarsson C, Bjerke M, Andersson B, Blennow K, Zetterberg H, Aberg ND, Olsson B, Eckerström C, Boke- mark L, Wallin A. Neuronal and glia-related biomarkers in cerebrospinal fluid of patients with acute ischemic stroke. J Cent Nerv Syst Dis. 2014 May; 6: 51-58.
 
48.
Ihle-Hansen H, Hagberg G, Fure B, Thommessen B, Fagerland MW, Øksengård AR, Engedal K, Selnes P. Association between total-Tau and brain atrophy one year after first-ever stroke. BMC Neurol. 2017 Jun; 17(1): 107.
 
49.
Brown GC. Neuronal loss after stroke due to microglial phagocytosis of stressed neurons. Int J Mol Sci. 2021 Dec; 22(24): 13442.
 
50.
Schaapsmeerders P, van Uden IW, Tuladhar AM, Maaijwee NA, van Dijk EJ, Rutten-Jacobs LC, Arntz RM, Schoonderwaldt HC, Dorresteijn LD, de Leeuw FE, Kessels RP. Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults. Hum Brain Mapp. 2015; 36(7): 2432-2442.
 
51.
Zhang J, Rui YC, Yang PY, Lu L, Li TJ. C-reactive protein induced expression of adhesion molecules in cultured cerebral microvascular endothelial cells. Life Sci. 2006; 78: 2983-2988.
 
52.
Kuhlmann CR, Librizzi L, Closhen D, Pflanzner T, Lessmann V, Pietrzik CU, de Curtis M, Luhmann HJ. Mechanisms of C-reactive protein-induced blood-brain barrier disruption. Stroke. 2009 Apr; 40(4): 1458-1466.
 
53.
Bi M, Gladbach A, van Eersel J, Ittner A, Przybyla M, van Hummel A, Chua SW, van der Hoven J, Lee WS, Müller J, Parmar J, Jonquieres GV, Stefen H, Guccione E, Fath T, Housley GD, Klugmann M, Ke YD, Ittner LM. Tau exacerbates excitotoxic brain damage in an animal model of stroke. Nat Commun. 2017 Sep; 8(1): 473.
 
54.
Skarabis H, Torzewski J, Ries W, Heigl F, Garlichs CD, Kunze R, Sheriff A. Sustainability of C-reactive protein apheresis in acute myocardial infarction-results from a supplementary data analysis of the exploratory C-reactive protein in acute myocardial infarction-1 study. J Clin Med. 2022 Oct; 11(21): 6446.
 
55.
Jiang X, Andjelkovic AV, Zhu L, Yang T, Bennett MVL, Chen J, Keep RF, Shi Y. Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog Neurobiol. 2018 Apr-May; 163-164: 144-171.
 
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