Italian Study Finds That COVID-19 Brain Fog Is Due To SARS-CoV-2 Infecting Neuronal Cells And Triggering Tau Protein Phosphorylation And Aggregation!
: The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought about unprecedented global health challenges since its outbreak in March 2020. While the primary respiratory symptoms of COVID-19 have been extensively documented, an emerging concern is the virus's impact on the central nervous system (CNS), leading to a range of neurological symptoms, including cognitive impairments often referred to as "brain fog." Numerous studies and COVID-19 News
reports have already shown that brain fog is a growing problem in the acute COVID-19 infection phase as well as in the post-COVID-19 phases. Additionally, there is mounting evidence linking SARS-CoV-2 infection to the exacerbation of Alzheimer's disease and an increased risk of developing this neurodegenerative condition.
SARS-Cov2 infects human neuron–like cells. Viruses detected in infected cells. A) Viral proteins detected in cellular extracts of infected and control cells by immunoblot. B) Superresolution imaging of viral particles detected in infected SH-SY5Y cells 48-h postinfection (hpi). SARS-CoV-2 Spike (S), tubulin (Tub), and DAPI (nuclei). C) Immunoblot of virions released 24- and 48 hpi in the supernatant of SH-SY5Y cells infected with B.1 or B.1.1.7 strains. Total Tau has been detected by anti Tau-13 antibodies. D) Superresolution imaging of infected cells. SARS-CoV-2 (S), Tau, and DAPI (nuclei). Scale bar: 10 µm
A new groundbreaking Italian study conducted by researchers from the Italian National Research Council (CNR), University of Pisa, University of Verona, University of Siena, and the University Hospital of Pisa has uncovered the rile of Tau proteins in COVID-19 induced Brain Fog. The study delves into the molecular mechanisms that connect SARS-CoV-2 infection with neurological symptoms and the development of Alzheimer's disease, shedding light on the role of Tau proteins in COVID-19-related brain fog.
SARS-CoV-2 and its Impact on the CNS
Early in the pandemic, it became evident that SARS-CoV-2 could infiltrate various organs, including the central nervous system, leading to a wide array of neurological symptoms. These symptoms encompassed alterations in smell and taste, persistent fatigue, headaches, attention deficits, and cognitive impairment, commonly referred to as "brain fog." Importantly, these neurological manifestations were not limited to severe COVID-19 cases but were also observed in individuals with mild symptoms.
The connection between SARS-CoV-2 and Alzheimer's disease has become increasingly apparent. COVID-19 not only worsens Alzheimer's symptoms in patients already diagnosed with the disease but also increases the risk of developing Alzheimer's in individuals who have recovered from COVID-19. These associations have raised questions about the molecular mechanisms underlying these effects on neuronal cells.
Tau Protein Hyperphosphorylation: A Key Finding
To unravel the intricate relationship between SARS-CoV-2
and neurological symptoms, the Italian research team conducted a series of experiments using human neuroblastoma cell cultures and mice infected with various SARS-CoV-2 strain variants. Their primary focus was on Tau proteins, which are integral to the normal functioning of neurons but are also known to accumulate in tangles and clumps in the brains of Alzheimer's patients.
The study's pivotal discovery was that SARS-CoV-2 infection resulted in the hyperphosphorylation of Tau proteins at specific pathological epitopes. These epitopes are binding sites for antibodies and are associated with Alzheimer's disease and other tauopathies. Tau hyperphosphorylation is a crucial step in the development of pathological aggregates of the protein, which are central to the neurodegenerative process.
Moreover, the researchers observed a substantial increase in the insoluble fraction of Tau proteins in infected cells. This alteration in Tau's biochemical properties is another hallmark of Alzheimer's disease. However, it remains unclear whether these changes in Tau are a direct consequence of the virus's actions or part of a cellular defense response aimed at limiting viral replication.
Further investigations into the molecular interactions revealed that SARS-CoV-2 interacts directly with Tau proteins in neuronal cells. This interaction may contribute to the hyperphosphorylation and subsequent aggregation of Tau. Notably, this finding supports the hypothesis that SARS-CoV-2 infection in the CNS triggers mechanisms that disrupt Tau function, ultimately impairing neuronal activity.
Tau's Role in Alzheimer's and COVID-19
Hyperphosphorylated Tau proteins have long been associated with Alzheimer's disease and other neurodegenerative conditions. These pathological changes in Tau's structure disrupt its interaction with microtubules, leading to the formation of insoluble aggregates. These aggregates are toxic to neurons and are a central driver of tauopathies.
The study also raised questions about the mechanism by which SARS-CoV-2 induces Tau hyperphosphorylation. It is likely that the virus's infection of neurons activates various kinases responsible for phosphorylating Tau or inhibits phosphatases that would otherwise counteract this phosphorylation. Additionally, inflammatory pathways activated by the virus may contribute to these neurological changes.
In conclusion, the Italian study provides crucial insights into the molecular mechanisms linking SARS-CoV-2 infection to COVID-19-related brain fog and its potential contribution to the development or exacerbation of Alzheimer's disease.
Understanding the long-term consequences of COVID-19 on neurological health is essential. Clinicians and researchers must remain vigilant in investigating the downstream effects of SARS-CoV-2 infection in neuronal cells to develop strategies for treatment and prevention of these debilitating conditions. As we navigate the ongoing challenges of the pandemic, this research underscores the importance of addressing both the acute and long-term impacts of COVID-19 on global health.
The study findings were published in the peer reviewed journal: PNAS Nexus.
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