Two New Studies Shows SARS-Cov-2 Infections Will Ultimately Lead To Enhanced Risk Of Developing Neurodegenerative Diseases Like Alzheimer’s Or Parkinson’s Disease!
: Already there is so much mounting evidence that SARS-CoV-2 infections and the COVID-19 disease will lead to an array of neurological issues but recently more studies are popping up detailing the mechanisms and also providing clinical evidence that SARS-CoV-2 infections will ultimately lead to the enhanced risk of developing various neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and Dementia.
News reviews two latest studies that have emerged showing a correlation between SARS-CoV-2 infection and the increased risk of developing such neurodegenerative diseases.
In the first study lead by researchers from Columbia University-New York-USA, it was found that brain changes that accompanies people as a result of a SARS-CoV-2 infection, leading to the development the COVID-19 disease shows parallels with Alzheimer's Disease.
The study findings may point to potential mechanism for brain fog in people with long COVID.
The study based on autopsies of 10 people who died with COVID-19 showed that the brains of COVID-19 patients had some of the same pathological changes seen in Alzheimer's disease, which may explain the memory issues individuals with long COVID experience.
study findings linked the inflammatory response found in SARS-CoV-2 infection with pathways causing tau hyperphosphorylation typically associated with Alzheimer's disease.
Co-author, Dr Andrew Marks, MD, of Columbia University told Thailand Medical News, “The study findings also indicated a role for leaky ryanodine receptor 2 (RyR2) in the pathophysiology of SARS-CoV-2 infection.”
Dr Mark further added, "The study findings show that long COVID-19 brain fog may be a form of Alzheimer's disease, but much more research needs to be done before we can make more definitive conclusions.”
Dr Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, who wasn't involved with the study commented on the study findings,"The major strength of the paper is that they identified abnormalities in several molecules which help characterize the neuroglial dysfunction in these patients at a biochemical level. However, no histology was performed for Alzheimer's type pathology and the implications for development of Alzheimer's disease would be hard to extrapolate from this study.”
The study findings were published in the peer reviewed journal: Alzheimer’s & Dementia. https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12558
It should be noted that defective ryanodine receptors have been implicated in diverse processes, including heart and lung disease. Inside neurons, they previously have been linked to an increase in phosphorylated tau.
The persistent of bra
in fog and cardiac symptoms in individuals with COVID-19 led Dr Marks and the other co-authors to investigate how ryanodine receptors were affected in COVID-19.
Dr Mark said, "What we found is really, I think, quite unexpected. Not only did we find defective ryanodine receptors in the hearts and lungs of deceased COVID patients, we also found them in their brains."
The study team analyzed signaling molecules in brain lysates of COVID-19 patients and controls and found evidence linking SARS-CoV-2 infection to activation of TGF-β signaling and oxidative overload. They also found high levels of phosphorylated tau in COVID-19 patients' brains, both in areas where tau is typically located in Alzheimer's and in other sites. No changes in pathways leading to amyloid beta formation were seen.
The study findings may imply that a COVID-19 immune response causes brain inflammation which leads to dysfunctional ryanodine receptors and altered cellular calcium dynamics, then to increases in phosphorylated tau.
Dr Marks added, "We propose a potential mechanism that may contribute to the neurological complications caused by SARS-CoV-2 ie a defective intracellular Ca2+ regulation and activation of Alzheimer's disease-like neuropathology.”
The study team commented that leaky RyR2 channels may be a therapeutic target to ameliorate some of the cognitive defects associated with SARS-CoV-2 infection and long COVID.
Interestingly, laboratory studies that treated COVID-19 patient brain samples with a drug targeting RyR2 channels prevented the calcium leak. The treatment, known as ARM210, currently is undergoing clinical testing at NIH for RyR1-related myopathy. https://clinicaltrials.gov/ct2/show/NCT04141670
Dr Mark added, "Future experiments will explore calcium channels as a potential therapeutic target for the neurological complications associated with COVID-19.”
In the second study by researchers from Thomas Jefferson University-USA, East Carolina University-USA and New York University-USA, it was found that SARS-CoV-2 infection enhances susceptibility to oxidative-stress induced parkinsonism.
Viral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic.
Considering the similarities in the systemic responses following SARS-CoV-2 infection with those observed after pandemic influenza, there is a question if a similar syndrome of post-encephalic parkinsonism could follow COVID-19 infection.
The study team wanted to determine if prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism.
In the study, hACE2 mice were infected with SARS-CoV-2 to induce mild to moderate disease. After 31 days recovery, mice were administered a non-lesion inducing dose of the parkinsonian toxin MPTP.
Subsequent neuroinflammation and SNpc dopaminergic neuron loss was determined and compared to SARS-CoV-2 or MPTP alone.
The study findings showed that hACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss following MPTP.
However, in mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc dopaminergic neurons than SARS-CoV-2 or MPTP, respectively (p < 0.05).
Detailed examination of microglial activation showed a significant increase in the number of activated microglia in the SARS-CoV-2 + MPTP group compared to SARS-CoV-2 or MPTP alone.
The study findings have important implications for long-term public health, given the number of individuals that have survived SARS-CoV-2 infection as well as for future public policy regarding infection mitigation. However, it will be critical to determine if other agents known to increase risk of Parkinson’s Disease also have synergistic effects with SARS-CoV-2 and if are abrogated by vaccination.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2022.02.02.478719v1
It should be noted that the role of the influenza virus H1N1 as a susceptibility agent has been recently validated in a retrospective study examining risk for developing Parkinson’s disease in humans following influenza. https://pubmed.ncbi.nlm.nih.gov/34694344/
Shockingly that study showed that previous influenza infection resulted in the risk for developing Parkinson’s disease increased by 173% compared to individuals not infected. This increase susceptibility was within the confidence interval determined epidemiologically for individual born during the time of the 1918 H1N1 pandemic. https://pubmed.ncbi.nlm.nih.gov/9158282/
The current preclinical studies examining SARS-CoV-2 infection suggest the possibility of a similar transient increase in parkinsonian incidence. Worryingly should this risk manifest, the diverse consequences would represent a great burden on patients, families, and society.
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