Petric_2025_Chem.Biol.Interact_15ChEPon_422_111787

The enzyme paraoxonase 1 (PON1) is present in high density lipoprotein (HDL) particles in blood plasma and in cerebrospinal fluid (CSF). Its activity has been investigated in several oxidative-stress-related conditions, including Alzheimer's disease (AD). There is convincing evidence that PON1 activity in blood is lower in AD patients than in healthy controls, but it is less clear whether there is a difference between the precursor stage of AD, known as mild cognitive impairment (MCI AD), and the dementia stage of AD. In the present study, we assessed PON1 status in blood plasma and cerebrospinal fluid (CSF) of 32 patients with MCI AD, 56 patients with AD dementia, and 74 patients with non-AD dementia. We measured PON1 concentration as well as rates of hydrolysis and Michaelis-Menten kinetic parameters K(m) and V(max) of PON1 for lactonase, arylesterase and arildialkylphosphatase activities in all the samples. There was no significant difference between AD dementia and MCI AD patients in any of the parameters measured. Within the AD group, we found that in blood plasma, rates of hydrolysis and V(max) negatively correlated with age in the case of lactonase and arylesterase. In CSF, the negative correlation with age for these parameters was even more pronounced. The correlation between age and PON1 status was more prominent in men for blood plasma and in women for CSF. The correlation between age and PON1 status was mostly absent in patients with other kinds of dementia, suggesting that PON1 activity decline is a part of development of AD pathology.