Epidemiological evidence that Alzheimer’s disease and Parkinson’s disease can be the result of viral infection


Several studies have indicated that bacterial or viral infections can lead to neurodegenerative disease. A recent study published in the journal nervous It focused on assessing putative associations between exposure to viruses and the onset of neurodegenerative disease (NDD), using real-world biobank scale data.

Study: Virus exposure and neurodegenerative disease risk across national biobanks.  Image credit: picmedical/Shutterstock

Study: Virus exposure and neurodegenerative disease risk across national biobanks. Image credit: picmedical/Shutterstock

background

A previous study suggested that previous infection with Epstein-Barr virus (EBV) increased the risk of developing multiple sclerosis. In addition, evidence regarding the short- and long-term cognitive effect of SARS-CoV-2 virus, the causative agent of the ongoing pandemic, has re-posed the question of a locus association. Between viral infection and neurodegenerative disease. Previous studies have also suggested a possible association between exposure to microbes and an increased risk of neurodegeneration.

About the study

The current study obtained relevant data from the FinnGen Project and the UK Biobank (UKB) to investigate the potential link between viral exposure and the incidence of several NDDs, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), vascular dementia (VAS), and multiple sclerosis. (MS), Parkinson’s disease (PD), and generalized dementia (DEM).

The two national biobanks, i.e. FinnGen and UKB, represented a large number of participants. FinnGen (Finnish nationwide biobank) contains genotyping data for over 300,000 individuals, while UKB contains genotyping data for nearly 500,000 individuals from the United Kingdom. For controls, a subset of 96,390 age-matched (over 60 years), unrelated individuals who shared European ancestry and did not have NDD of any kind were included.

Results

Based on longitudinal data from FinnGen, 45 significant associations with NDD virus/virus were found, and 22 of these associations were replicated in cross-sectional data from UKB. Notably, influenza, with or without the development of pneumonia, was identified as the most common viral infection, resulting in five of the six NDDs mentioned above, such as AD, ALS, dementia, PD, and VAS.

Viral encephalitis caused by varicella zoster virus has also been associated with more onset of NDD. An association of HSV encephalitis with Alzheimer’s disease, genital warts, dementia, hepatitis, Alzheimer’s disease, EBV, MS, EBV and dementia, HSV, and multiple sclerosis was found in this study.

A recent Danish study revealed an association between influenza and Parkinson’s disease, with an odds ratio estimated at 1.73 for up to 10 years of viral infection. Interestingly, a similar observation was drawn based on the FinnGen cohort, where the hazard ratio for influenza and pneumonia was estimated to be 1.72.

In this study, none of the viruses were found to be associated with a protective effect, as they were all associated with an elevated risk of developing NDD. About 81% of the viruses were found to be neurotrophic, which indicates that they can attack the central nervous system (CNS) via peripheral nerves or by crossing the blood-brain barrier. These viruses increase the risk of NDD by reducing cognitive reserve through inflammation in the brain.

Effective vaccines are available for many types of viral infections, such as influenza, varicella zoster (shingles), and pneumonia. Although many vaccines, such as the COVID-19 vaccine, do not prevent the disease from occurring, they do reduce the severity of the disease. Importantly, several studies have provided evidence that vaccination significantly reduces the risk of developing NDD.

Vaccination may reduce transmission of the virus and reduce infection burden or viral load, and prevent the abnormal immune reaction, which may affect the pathogenesis of NDD. Increased use of widely available vaccines could help reduce the overall risk of developing NDD in later stages of life. However, for its implementation, more research is needed to evaluate the effectiveness of different types of vaccines.

In addition to vaccination, antiviral treatment for herpes simplex virus and varicella zoster virus has also been shown to reduce the risk of dementia. Although targeted antiviral drugs also prevented the development of NDD, more research needs to be done to better understand its mechanism and effect.

Study limitations

The current study has some limitations, including access to the FinnGen summary data level only. In addition, the authors only had access to cross-sectional and pathological data scattered in the UKB. This limitation in data access can cause some confusion in data analysis. Also, both national cohorts used diagnoses based on medical billing codes and not blood or laboratory assays. Because the consolidation of electronic records only occurred in the past two decades, it is not possible to assess the effect of exposure to the virus early in life on the incidence of NDDs.

conclusions

A longitudinal and cross-sectional survey was performed to analyze the relationship between viral exposure and NDDs in an unbiased manner. Quick identification of potential factors that enhance the risk of developing NDD can also help formulate effective strategies to prevent the onset of the disease. In the future, more research needs to be done to better understand virus/NDD associations.





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