Abstract
Background: Paraoxonase 1 (PON1) functions to protect the cholinergic system against nerve gases and the organophosphate family of pesticides. Recent studies have shown that polymorphisms at the PON1 L55M and Q192R loci might affect individual susceptibility to experience-derived and environmental events such as the exposure to inhibitors of cholinesterase (ChEIs). Objective: ChEI therapy being the treatment of choice for mild-to-moderate Alzheimer’s disease (AD) patients, we determined whether genetic variations in the PON1 loci are associated with AD risk and whether they affect brain choline acetyltransferase (CHAT) activity, nicotinic receptor density, and β-amyloid (Aβ) levels in different regions of AD and age-matched control subjects. Methods: This pilot genetic study used a small cohort of brains from autopsy-confirmed AD patients and age-matched controls from the Douglas Hospital Brain Bank, Quebec, Canada. Results: The frequency of the M55M genotype at the PON1 L55M locus was found to be significantly increased in AD patients relative to age-matched controls (p < 0.05). Significant associations were observed between the PON1 L55M and Q192R polymorphisms and frontal cortex Aβ levels as well as CHAT activity and nicotinic receptor density in the temporal cortex. Conclusions: Our results suggest a prominent role for PON1 in the pathophysiology of common AD with a marked impact on the cholinergic system and Aβ levels in the brain.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
