Pathogens that contribute to the accumulation of infectious burden
Results published in 2015 in the European Journal of Neurology confirmed a link between infectious burden and AD. Findings suggest that infectious burdens are risk factors pre-onset and responsible for faster progression post-onset.7 Antibody titers of cytomegalovirus herpes simplex virus type 1 (HSV-1) (B burgdorferi, C pneumonia, and H pylori) were assessed using the ELISA serological test in patients with AD and a control group. In all cases, the infectious burden was positively associated with AD. Individuals who had higher infectious burdens and, consequently, increased serum Aβ levels were more affected with respect to cognitive deficits.
Bacteria, viruses, fungi, and, occasionally, protozoa are able to cross through the blood-brain barrier and in turn cause chronic illnesses. Various types of spirochetes (eg, B burgdorferi) and obligate intracellular bacteria (C pneumoniae) are among the most frequently invasive infectious entities that can generate persistent infection in the brain.3 In turn, this finding suggests that these pathogens could enhance the Aβ deposition in AD and trigger peripheral inflammation. Moreover, there is a suggestion that B burgdorferi causes intracellular inflammation in brain tissues, which leads to neurodegenerative and cognitive changes in people with neuroborreliosis and AD. H pylori- specific IgG antibody in serum is thought to be a marker for AD.8 However, further research is needed to detect the availability of these antibodies in the brain.
Viral burden of herpes simplex virus (HSV), human herpesvirus (HHV), and the hepatitis C virus (HCV) is commonly associated with AD by apolipoprotein E-ε4 (APOE-ε4).9 The accumulation of senile amyloid plaques and tau-protein is a significant risk in people with AD due to the combination with APOE-ε4. One of the biomarkers of HSV reactivation detected by ELISA showed a significant link between the presence of anti-HSV-1 IgG, anti-HSV-1 IgM antibodies, and AD.3 According to data from the Center for Disease Control and Prevention, one in three people aged 60 or over suffer from HHV.10 For this reason, shingles indicate a risk for future AD.
There are limited studies to explain the mechanisms that underlay HCV infection and dementia.
Two hypotheses have been advanced:
1) The virus causes the systemic inflammation and thereby contributes to indirect neurotoxicity;
2) The virus is able to disintegrate brain tissues through a direct cumulative neurotoxic effect.
Dr Aliev is President and Founder, International Research Institute, San Antonio, TX; Professor of Pharmacology, First Moscow State Medical University, Moscow; and Professor, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Russia. Dr Bachurin is Scientific Director and Professor of Chemistry, Institute of Physiologically Active Compounds, Russian Academy of Sciences. Ms Mikhaylenko is a PhD Student, Department of Pharmacology, Institute of Physiologically Active Compounds, Russian Academy of Sciences. Dr Bragin is President and Founder, Stress Relief and Memory Training Center, Brooklyn, NY. Dr Avila -Rodriguez is Leading Researcher, Health Sciences Faculty, Clinical Sciences Department, University of Tolima, Ibague, Colombia. Dr Somasundaram is Professor, Biology Department, Salem University, Salem, WV. Dr Kirkland is Professor, Biology Department and Executive Vice President, Salem University. Dr Tarasov is Chairman, Department of Pharmacology and Pharmacy, First Moscow State Medical University, Moscow. The authors report no conflicts of interest concerning the subject matter of this article.
Acknowledgments—This research was supported within the framework of the grant provided by CSP Ministry of the Health Russian Federation, and by the IPAC RAS State Targets Project # 0090-2019-0005; the Russian Academic Excellence Project “5-100” for the Sechenov University, in Moscow, Russia, also provided support for the research.
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