Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 1, January, p. 71–78

doi: 10.17219/acem/111377

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Paraoxonase 1 decline and lipid peroxidation rise reflect a degree of brain atrophy and vascular impairment in dementia

Iwona Bednarz-Misa1,A,B,D,F, Izabela Berdowska1,B,D,E,F, Marzena Zboch2,B,C,F, Błażej Misiak3,4,B,E,F, Bogdan Zieliński1,B,F, Sylwia Płaczkowska5,B,F, Mariusz Fleszar1,B,F, Jerzy Wiśniewski1,B,F, Andrzej Gamian1,A,E,F, Małgorzata Krzystek-Korpacka1,A,B,C,D,E,F

1 Department of Medical Biochemistry, Wroclaw Medical University, Poland

2 Alzheimer Center, Wroclaw Medical University, Ścinawa, Poland

3 Department of Psychiatry, Wroclaw Medical University, Poland

4 Department of Genetics, Wroclaw Medical University, Poland

5 Department of Professional Training in Clinical Chemistry, Wroclaw Medical University, Poland


Background. Paraoxonase 1 (PON1) is an enzyme with the capability to protect against lipid oxidation and atherosclerotic lesions formation. Impaired antioxidative capacity and enhanced lipid peroxidation (reflected by malondialdehyde rise) accompany dementias.
Objectives. The aim of this study was to discern the possible differences in the activity and phenotype distribution of PON1, and lipid peroxidation level in dementias of neurodegenerative and vascular pathology, to assess whether they reflect structural changes in the brain, and to evaluate their potential as dementia markers.
Material and Methods. Paraoxonase 1 arylesterase activity and polymorphisms (dual-substrate method), and malondialdehyde/thiobarbituric acid reactive substances (MDA/TBARS) levels were determined spectrophotometrically in 257 serum samples derived from 136 dementive patients (with Alzheimer’s disease (AD; n = 63), vascular dementia (VaD; n = 40) and mixed-type dementia (MD; n = 33), as well as from 121 non-dementive individuals. The results were analyzed with reference to dementia type and severity (assessed with Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scales), structural brain changes (estimated with magnetic resonance imaging (MRI) – Global Cortical Atrophy (GCA), Medial Temporal lobe Atrophy (MTA) and Fazekas scales)) and brain ischemia (Hachinski Ischemic Scale (HIS) index), and evaluated using receiver operating characteristic (ROC) analysis.
Results. Malondialdehyde/thiobarbituric acid reactive substances were increased in dementia (more in VaD than AD). In patients with vascular involvement, MDA/TBARS elevation reflected a degree of global cortical atrophy. Paraoxonase 1 activity was decreased in patients with dementia, especially in patients with severe cognitive deficits. In VaD, a drop in PON1 reflected a degree of MTA and brain ischemia. MDA/TBARS displayed 75% accuracy as a general dementia marker, but, similarly to PON1, were a poor differential marker.
Conclusion. Both indices were more associated with vascular involvement and the severity of brain atrophy or ischemia rather than with degree of cognitive decline.

Key words

Alzheimer’s disease, vascular dementia, paraoxonase 1, mixed-type dementia, MDA/TBARS

References (40)

  1. Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016;12(4):459–509.
  2. Ahotupa M. Oxidized lipoprotein lipids and atherosclerosis. Free Radic Res. 2017;51(4):439–447. doi:10.1080/10715762.2017.1319944
  3. Luca M, Luca A, Calandra C. The role of oxidative damage in the pathogenesis and progression of Alzheimer’s disease and vascular dementia. Oxid Med Cell Longev. 2015;2015:504678. doi:10.1155/2015/504678
  4. Schrag M, Mueller C, Zabel M, et al. Oxidative stress in blood in Alzheimer’s disease and mild cognitive impairment: A meta-analysis. Neurobiol Dis. 2013;59:100–110. doi:10.1016/j.nbd.2013.07.005
  5. Chistiakov DA, Melnichenko AA, Orekhov AN, Bobryshev YV. Paraoxonase and atherosclerosis-related cardiovascular diseases. Biochimie. 2017;132:19–27. doi:10.1016/j.biochi.2016.10.010
  6. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000. doi:10.1002/jps.3080051129
  7. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS–ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939–944. doi:10.1037/0894-4105.19.4.520
  8. World Health Organization. International Statistical Classification of Diseases and Related Health Problems, 10th Revision. Vol 41. Geneva, Switzerland: World Health Organization; 1992.
  9. Erkinjuntti T. Clinical criteria for vascular dementia: The NINDS-AIREN criteria. Dement Geriatr Cogn Disord. 1994;5(3–4):189–192. doi:10.1159/000106721
  10. Hachinski V, Iliff L, Zilhka E, et al. Cerebral blood flow in dementia. Arch Neurol. 1975;32(9):632–637. doi:10.1001/archneur.1975.00490510088009
  11. Wahlund LO, Westman E, van Westen D, et al. Imaging biomarkers of dementia: Recommended visual rating scales with teaching cases. Insights Imaging. 2017;8(1):79–90. doi:10.1007/s13244-016-0521-6
  12. Vellas B, Villars H, Abellan G, et al. Overview of the MNA: Its history and challenges. J Nutr Heal Aging. 2006;10(6):456–463.
  13. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–194. doi:10.1111/j.1365-2796.2004.01388.x
  14. Rice-Evans CA, Diplock AT, Symons MCR. Techniques in free radical research. In: Burdon RH, van Knippenberg PH, eds. Laboratory Techniques in Biochemistry and Molecular Biology. Vol. 22. Amsterdam, the Netherlands: Elsevier Science Publishers BV; 1991:1–291. doi:10.1016/S0075-7535(08)70046-9
  15. Bartosz G. The Other Face of Oxygen. Free Radicals in the Environment [in Polish]. Warszawa, Poland: PWN; 2004.
  16. Costa LG, Vitalone A, Cole TB, Furlong CE. Modulation of paraoxonase (PON1) activity. Biochem Pharmacol. 2005;69(4):541–550. doi:10.1016/j.bcp.2004.08.027
  17. La Du BN, Billecke S, Hsu C, Haley RW, Broomfield CA. Serum paraoxonase (PON1) isozymes: The quantitative analysis of isozymes affecting individual sensitivity to environmental chemicals. Drug Metab Dispos. 2001;29(4 Pt 2):566–569.
  18. Charlton-Menys V, Liu Y, Durrington PN. Semiautomated method for determination of serum paraoxonase activity using paraoxon as substrate. Clin Chem. 2006;52(3):453–457. doi:10.1373/clinchem.2005.063412
  19. Massaad CA. Neuronal and vascular oxidative stress in Alzheimer’s disease. Curr Neuropharmacol. 2011;9(4):662–673. doi:10.2174/157015911798376244
  20. Polidori MC, Mattioli P, Aldred S, et al. Plasma antioxidant status, immunoglobulin G oxidation and lipid peroxidation in demented patients: Relevance to Alzheimer disease and vascular dementia. Dement Geriatr Cogn Disord. 2004;18(3–4):265–270. doi:10.1159/000080027
  21. Casado A, Encarnación López-Fernández M, Concepción Casado M, de La Torre R. Lipid peroxidation and antioxidant enzyme activities in vascular and Alzheimer dementias. Neurochem Res. 2008;33(3):450–458. doi:10.1007/s11064-007-9453-3
  22. Gustaw-Rothenberg K, Kowalczuk K, Stryjecka-Zimmer M. Lipids’ peroxidation markers in Alzheimer’s disease and vascular dementia. Geriatr Gerontol Int. 2010;10(2):161–166. doi:10.1111/j.1447-0594.2009.00571.x
  23. Lopez-Riquelme N, Alom-Poveda J, Viciano-Morote N, Llinares-Ibor I, Tormo-Diaz C. Apolipoprotein E ε4 allele and malondialdehyde level are independent risk factors for Alzheimer’s disease. SAGE Open Med. 2016;4:2050312115626731. doi:10.1177/2050312115626731
  24. Bednarska-Makaruk M, Graban A, Lipczyńska-Łojkowska W, et al. Positive correlation of paraoxonase 1 (PON1) activity with serum insulin level and HOMA-IR in dementia: A possible advantageous role of PON1 in dementia development. J Neurol Sci. 2013;324(1–2):172–175. doi:10.1016/j.jns.2012.11.003
  25. Wehr H, Bednarska-Makaruk M, Graban A, et al. Paraoxonase activity and dementia. J Neurol Sci. 2009;283(1–2):107–108. doi:10.1016/j.jns.2009.02.317
  26. Cervellati C, Romani A, Bergamini CM, et al. PON-1 and ferroxidase activities in older patients with mild cognitive impairment, late onset Alzheimer’s disease or vascular dementia. Clin Chem Lab Med. 2015;53(7):1049–1056. doi:10.1515/cclm-2014-0803
  27. Castellazzi M, Trentini A, Romani A, et al. Decreased arylesterase activity of paraoxonase-1 (PON-1) might be a common denominator of neuroinflammatory and neurodegenerative diseases. Int J Biochem Cell Biol. 2016;81:356–363. doi:10.1016/j.biocel.2016.06.008
  28. Paragh G, Balla P, Katona E, Seres I, Égerházi A, Degrell I. Serum paraoxonase activity changes in patients with Alzheimer’s disease and vascular dementia. Eur Arch Psychiatry Clin Neurosci. 2002;252(2):63–67. doi:10.1007/s004060200013
  29. Dantoine TF, Debord J, Merle L, Lacroix-Ramiandrisoa H, Bourzeix L, Charmes JP. Paraoxonase 1 activity: A new vascular marker of dementia? Ann N Y Acad Sci. 2002;977:96–101. doi:10.1111/j.1749-6632.2002.tb04802.x
  30. Cervellati C, Trentini A, Romani A, et al. Serum paraoxonase and arylesterase activities of paraoxonase-1 (PON-1), mild cognitive impairment, and 2-year conversion to dementia: A pilot study. J Neuro­chem. 2015;135(2):395–401. doi:10.1111/jnc.13240
  31. Arslan A, Tüzün FA, Arslan H, et al. The relationship between serum paraoxonase levels and carotid atherosclerotic plaque formation in Alzheimer’s patients. Neurol Neurochir Pol. 2016;50(6):403–409. doi:10.1016/j.pjnns.2016.07.002
  32. Torres LL, Quaglio NB, De Souza GT, et al. Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer’s disease. J Alzheimer’s Dis. 2011;26(1):59–68. doi:10.3233/JAD-2011-110284
  33. Balmuș I-M, Strungaru S-A, Ciobica A, et al. Preliminary data on the interaction between some biometals and oxidative stress status in mild cognitive impairment and Alzheimer’s disease patients. Oxid Med Cell Longev. 2017;2017:1–7. doi:10.1155/2017/7156928
  34. Liu Z, Liu Y, Tu X, et al. High serum levels of malondialdehyde and 8-OHdG are both associated with early cognitive impairment in patients with acute ischaemic stroke. Sci Rep. 2017;7:9493. doi:10.1038/s41598-017-09988-3
  35. Bulboacă AE, Bulboacă SD, Bulboacă AC, Prodan CI. Association between low thyroid-stimulating hormone, posterior cortical atrophy and nitro-oxidative stress in elderly patients with cognitive dysfunction. Arch Med Sci. 2017;13(5):1160–1167. doi:10.5114/aoms.2016.60129
  36. Praticò D, Uryu K, Leight S, Trojanoswki JQ, Lee VM-Y. Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci. 2001;21(12):4183–4187. doi:21/12/4183 [pii]
  37. Martín-Aragón S, Bermejo-Bescós P, Benedí J, et al. Metalloproteinase’s activity and oxidative stress in mild cognitive impairment and Alzheimer’s disease. Neurochem Res. 2009;34(2):373–378. doi:10.1007/s11064-008-9789-3
  38. Marsillach J, Parra S, Coll B, Joven J, Camps J. Paraoxonase-1 in chronic liver diseases, neurological diseases and HIV infection. In: Mackness B, Mackness M, Aviram M, Paragh G, eds. The Paraoxonases: Their Role in Disease Development and Xenobiotic Metabolism. Dordrecht, the Netherlands: Springer; 2008:187–198.
  39. Wilkinson D, Francis P, Schwam E, Payne-Parrish J. Cholinesterase inhibitors used in the treatment of Alzheimer’s disease. Drugs Aging. 2004;21(7):453–478. doi:10.2165/00002512-200421070-00004
  40. Draganov DI, La Du BN. Pharmacogenetics of paraoxonases: A brief review. Naunyn Schmiedebergs Arch Pharmacol. 2004;369(1):78–88. doi:10.1007/s00210-003-0833-1