Abstract
Alzheimer's disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extracellular matrix proteins and basement membrane compounds. In the brain, the pathological role of MMPs includes the disruption of the blood-brain barrier leading to the induction of neuroinflammation. Among various MMPs, MMP-2 and MMP-3 belong to candidate molecules related to AD pathology. In our study, we aimed to evaluate the association of MMP2 rs243865 and MMP3 rs3025058 polymorphisms with AD susceptibility and their influence on age at onset and MoCA score in patients from Slovakia. Both MMP gene promoter polymorphisms were genotyped in 171 AD patients and 308 controls by the PCR-RFLP method. No statistically significant differences in the distribution of MMP2 rs243865 (-1306 C>T) and MMP3 rs3025058 (-1171 5A>6A) alleles/genotypes were found between AD patients and the control group. However, correlation with clinical findings revealed later age at disease onset in MMP2 rs243865 CC carriers in the dominant model as compared to T allele carriers (CC vs. CT+TT: 78.44 ± 6.28 vs. 76.36 ± 6.39, p = 0.036). The results of MMP3 rs3025058 analysis revealed that 5A/6A carriers in the overdominant model tended to have earlier age at disease onset as compared to other MMP3 genotype carriers (5A/6A vs. 5A/5A+6A/6A: 76.61 ± 5.88 vs. 78.57 ± 6.79, p = 0.045). In conclusion, our results suggest that MMP2 rs243865 and MMP3 rs3025058 promoter polymorphisms may have influence on age at onset in AD patients.
Highlights
Alzheimer’s disease (AD) is a chronic neurodegenerative disease of the central nervous system characterized by progressive memory loss, confusion, and cognitive dysfunction
The mean age at examination was significantly higher in the AD group than in controls (79.68 versus 76.23 years; p < 0:0001), while an opposite trend was observed for the Montreal Cognitive Assessment (MoCA) score having a lower value in AD patients (14.54 versus 27.52; p < 0:0001)
Among various Matrix metalloproteinases (MMPs), MMP-2 and MMP-3 belong to candidate molecules involved in AD pathogenesis
Summary
Alzheimer’s disease (AD) is a chronic neurodegenerative disease of the central nervous system characterized by progressive memory loss, confusion, and cognitive dysfunction. It is the cause of 60 to 70% of dementia cases. The AD prevalence is estimated at 4.4% in people aged 65 years to 22% in people aged 90 years and older [1]. There are two types of AD: early-onset AD that manifests in people under the age of 65 and the much more common late-onset AD that affects people over 65. The major risk factors for AD are advanced age, genetic predisposition, chronic diseases, head injuries, and other factors [2]. The histopathological characteristics in the AD brain include senile plaques composed of the extracellular accumulation of the amyloid β peptide and intraneuronal fibrillar aggregates of hyperphosphorylated tau proteins [3, 4]
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