Analysis of genetic variants TREM2 and plasma gingipain K and R level in patients with Alzheimer’s disease
Mikolaj Hurla, Natalia Banaszek, Jolanta Florczak‐Wyspianska, Olivia Michalczyszyn, Wojciech Owecki, Wojciech Kozubski, Jolanta DorszewskaAbstract
Background
Alzheimer’s disease (AD) is characterized by an acquired, progressive impairment of cognitive functions. The pathogenesis of this disease remains unknown. It is explained based on the following theories: amyloid cascade, inflammation, vascular, and infection hypothesis. Recently hypothesized that Porphyromonas gingivalis may be a unifying factor linking the different hypotheses related to AD pathogenesis. P. gingivalis produces cysteine proteinases called gingipain K and gingipain R, which are virulence factors. P. gingivalis plays a significant role in periodontitis. Periodontitis is provoked by bacterial lipopolysaccharide, which then leads to an immune response. The TREM2 gene is involved in the immune response. P. gingivalis may be responsible for reducing the expression of the TREM2 gene and TREM2 protein. TREM2 protein deficiency may impair Aß degradation, which may significantly increase the risk of AD. It has been showed a tendency for earlier onset of symptoms and faster progression of AD in people who were carriers of the potentially pathogenic TREM2 (rs143332484) CT variant of this gene. The study aimed to analyze plasma gingipain K and R concentration and TREM2 (rs143332484) genetic variants in AD patients, control subjects related to AD cases (CR), and control subjects without a family history of AD (CU).
Method
The studies were conducted on 74 subjects (AD and controls). The TREM2 genotype was determined by HRM and sequencing. The gingipain K and R concentrations were determined by the ELISA method.
Results
The highest concentration of gingipain K (p = 0.0820) and R (p = 0.0740) was found in AD compared to CR, and CU. The TREM2 CT genotype was most common in AD patients. Patients with this genotype had the highest concentration of gingipain K. However, AD patients with the TREM2 CC genotype showed statistically significantly higher concentrations of gingipain R (p<0.05) compared to CR and CU.
Conclusion
It seems that both gingipains K and R may be involved in the pathogenesis of AD.