UNDERSTANDING THE CNS AND PERIPHERAL NERVOUS SYSTEM PATHOLOGY OF COVID AND LONG COVID FROM AN ALZHEIMER’S PERSPECTIVE: A HYPERACCELERATED HYBRID OF ALZHEIMER’S (AD) AND PARKINSON’S DISEASE (PD)
The Spike Protein and the systemic hyperphosphorylation of Tau
MY MOST IMPORTANT FINDING TO DATE.
It was once believed that Amyloid plaques were the cause of Alzheimer’s Disease. However, it has since been discovered that the PRESENCE of Amyloid greatly ACCELERATES the deposition of Tau. This is most likely why the elderly, and those that have certain Amyloid-expressing conditions, experience more severe disease. This may also be why some develop Long COVID, while others do not. As an aside, I am concerned that repeated exposure to the Spike Protein may accelerate the seeding process. For example, advancing the Amyloid/Tau state of a 20 year old to that of a 30 year old, etc. per exposure.
The first question we should ask ourselves is, why is Tau the “villain” in this story? The reason is that it is one of the Intrinsically Disordered Proteins (IDP) in the human body.
IDPs are able to cause hyperphosphorylation. Please note that the S1/S2 cleavage site of the Spike Protein is NOT ONLY AN INTRINSICALLY DISORDERED PROTEIN, but the sequence at Spike S1/S2 site (the most disordered part) also enables cleavage by furin and phospho‑regulation in SARS‑CoV2 BUT NOT in SARS‑CoV1 or MERS‑CoV!
It is highly phosphorylated Tau which is toxic, neurodegenerative and fibril-producing. In AD, it has been observed that only 1% of Tau is of this hyperphosphorylated species.
This occurs through a process called liquid-liquid-phase-separation (LLPS). In it, the cell reacts by creating an organelle which AGGREGATES HYPERPHOSPHORYLATED TAU PERFECTLY! Also! You many not find amyloid! The process can occur without the presence of Amyloid. Yet, the presence of Amyloid seems to greatly enhance/accelerate the process.
What is occurring, I believe, is that the S Protein is inducing these organelles and hyperphosphorylating Tau. This would clearly explain the observed hyperphosphorylated Tau in the autopsies mentioned below.
HOWEVER! It is most important to understand that in COVID-19 autopsies, the neuronal cell death upon viral infection by SARS-CoV-2 was preceded by aberrant intraneuronal localisation and hyperphosphorylation of Tau protein, similar to the pathogenesis of Alzheimer's disease and other neurodegenerative diseases. Therefore, it is almost certain that FAR more than 1% of Tau is being hyperphosphorylated by SARS-CoV-2 infection/transfection.
Why do I say transfection?
Interactions between SARS-CoV-2 spike S protein and its receptor ACE2 similarly contributed to the spreading of cytosolic prions and Tau aggregates. Also, coculture with aggregate-bearing HEK donors overexpressing spike S increased aggregate induction in recipients.
Therefore, I believe the Spike Protein is inducing massive amounts of hyperphosphorylated Tau, which is creating the fibrils. This explains the AD, PD and even can explain the sudden cardiac deaths, as Tauopathies effect both the CNS and the peripheral autonomic nervous system.
PLEASE NOTE ABOVE. INDUCTION OF TAU VIA VIRUS. (Perhaps the net effect of the Spike Protein)
This should be stern warning of a clear and present danger which must be explored fully.
Walter, your brilliant, scarily prescient work is the reason #walterwasright trends on the twitter [and I use this hashtag to remind those late to your thinking’s party who was way out ahead...you!]. Deep gratitude to you.
My further research into brain fog last week found that the gp120 binds to tubilin isoforms and dysrupts microtubule assembly and the nerve cytoskeleton hence signalling & transport, eventually apoptosis....and mutations in tau suspected too. We arrived on the same page by different routes
"The control of the microtubule function is extremely complex, establishing and maintaining the architecture of the neuron. The control is distributed throughout the cell, which brings up the question of where the central control is to respond to mental events in such detailed and complex ways. They are highly regulated in terms of the number, length, allocation, exact positioning and placement. Abnormalities in any of these functions leads to brain disease.
Mutations in the proteins that hold the microtubules in place, such as tau are critical for the development of major neurodegenerative diseases (see post). The motors that move material along the microtubule highways—dyneins and kinesins—and regulators of these motors—dynactins—can produce other brain diseases. Defective transport in the axon is associated with ALS, Alzheimer’s, and multiple sclerosis."