Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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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

Abstract

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

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