Abstract
BackgroundRenin-angiotensin system (RAS) influences the central nervous system not only through its peripheral impact—the brain possesses its own local RAS. Studies showed altered RAS components in Parkinson’s disease (PD) and their association with oxidative stress which may be linked to neurodegeneration and dementia. Moreover, the protective functions of RAS blockade antagonists against cognitive decline and dementia have been suggested. This study aimed to examine whether genetic variability in RAS genes correlates with cognitive decline in PD.Methods and resultsWe genotyped single nucleotide polymorphisms (SNPs) in angiotensinogen (AGT: rs699, rs4762), angiotensin II receptors (AGTR1: rs5186 and AGTR2: rs5194, rs1403543) genes, as well as insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE I/D) gene in 256 PD patients, divided into three groups: without cognitive decline, with mild cognitive impairment and with PD dementia. We did not find any significant differences in the frequencies of the analysed polymorphisms in any of the groups.ConclusionsDespite no direct correlation between the investigated polymorphisms in RAS genes and cognitive decline in PD, we believe the impact of those genotypes may be indirect, affecting RAS blockade treatment.
Highlights
The impact of the renin-angiotensin system (RAS) on the central nervous system was originally considered by its influence on blood pressure and water and electrolyte balance since Renin-angiotensin system (RAS) components do not cross the blood–brain barrier [1]
Some components of RAS have been found to be altered in Parkinson’s disease (PD) patients: Angiotensin-converting enzyme (ACE) activity was increased in the cerebrospinal fluid and AT1R expression was decreased in the brain in a post-mortem study, which was associated with the loss of dopaminergic neurons [5, 6]
The induction of parkinsonian symptoms was observed in PD animal models by the use of a neurotoxin that increased NADPH expression and microglia activation; increased expression of NADPH:quinone oxidoreductase was observed in the substantia nigra pars compacta of PD patients, among whom many were described as having dementia [8, 9]
Summary
The impact of the renin-angiotensin system (RAS) on the central nervous system was originally considered by its influence on blood pressure and water and electrolyte balance since RAS components do not cross the blood–brain barrier [1]. Some components of RAS have been found to be altered in Parkinson’s disease (PD) patients: ACE activity was increased in the cerebrospinal fluid and AT1R expression was decreased in the brain in a post-mortem study, which was associated with the loss of dopaminergic neurons [5, 6]. Methods and results We genotyped single nucleotide polymorphisms (SNPs) in angiotensinogen (AGT: rs699, rs4762), angiotensin II receptors (AGTR1: rs5186 and AGTR2: rs5194, rs1403543) genes, as well as insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE I/D) gene in 256 PD patients, divided into three groups: without cognitive decline, with mild cognitive impairment and with PD dementia. Conclusions Despite no direct correlation between the investigated polymorphisms in RAS genes and cognitive decline in PD, we believe the impact of those genotypes may be indirect, affecting RAS blockade treatment
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