COVID-19 RNA Based Vaccines and the Risk of Prion Disease

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
benhadad
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Re: COVID-19 RNA Based Vaccines and the Risk of Prion Disease

Postby benhadad » Sun May 02, 2021 9:21 pm

While I appreciate the author of the paper bringing to the forefront a possible concern, I find the lack of reference to know current and urgent research on this topic to be a large distraction.

For example, TDP-43 without any prompting from vaccines has been implicated in ALS. This paper is similar to me saying, this new soap is so powerful it can cause your car to fall apart, without telling you the real issue being that the soap will dissolve rust. So my car will fall apart only if it is full of rust... not because of the soap....

What I would expect is that it is explained that this soap is effective in dissolving rust, since many cars in the northeast are being literally held together by rust, we recommend caution in using this soap without taking care of rust issues first. Instead, he blames the soap...



As far as TDP-43 and its effects on disease, the research is all over the board. And while current research points to it being involved in prion-related diseases, the reason for this is not normally linked to anything in relationship to RNA vaccines pathway.

https://onlinelibrary.wiley.com/doi/abs ... /ene.12706
https://sci-hub.do/10.1111/j.1365-2990.2008.00963.x
https://sci-hub.do/10.1016/j.celrep.2013.06.007
https://sci-hub.do/10.1016/j.nbd.2016.08.007

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Re: COVID-19 RNA Based Vaccines and the Risk of Prion Disease

Postby NF52 » Mon May 03, 2021 7:24 am

benhadad wrote:While I appreciate the author of the paper bringing to the forefront a possible concern, I find the lack of reference to know current and urgent research on this topic to be a large distraction.

For example, TDP-43 without any prompting from vaccines has been implicated in ALS.
...
As far as TDP-43 and its effects on disease, the research is all over the board. And while current research points to it being involved in prion-related diseases, the reason for this is not normally linked to anything in relationship to RNA vaccines pathway.
Welcome, benhadad!

Thank you for adding to the community's understanding of the TDP-43 protein, which is rarely mentioned in articles about the biomarkers of amyloid beta plaques and tau tangles that most people associate with Alzheimer's disease. I remember hearing about TDP-43 in a conference presentation and having a "wait, there's something ELSE to worry about?!" moment.

The info you shared shows the complexity of diseases of the brain, even when the resulting dementias or diseases may have similarities. Even more surprising, most people don't think of ALS (Lou Gehrig's disease) and Alzheimer's as being in any way connected genetically, yet they may both been influenced by TDP-43. This isn't simply a "who cares what the cause is?" issue. If an anti-amyloid or anti-tau drug is tried on people who appear to have Alzheimer's and it turns out that TDP-43 pathology is the cause, then the trial may be ineffective because the person being studied wasn't really someone with amyloid beta or tau.

I've added to your helpful links with a link explaining why it might be important to recognize TDP-43, not as triggering ALS or Alzheimer's after a COVID-vaccine, but as an important current area of research, in a 2020 article from Frontiers in Molecular Neuroscience: TDP-43: From Alzheimer’s Disease to Limbic-Predominant Age-Related TDP-43 Encephalopathy
Existing clinical trials are mostly aimed at patients with mild to moderate AD, and TDP-43 pathology is mostly seen in the oldest-old and those with a more severe clinical phenotype (Wilson et al., 2011; Robinson et al., 2014; Nelson et al., 2019); between 20% and 50% of AD cases, and 75% of severe cases exhibit pathophysiological TDP-43 (Amador-Ortiz et al., 2007; Uryu et al., 2008). Therefore, TDP-43 may be a potential target for the treatment of severe AD with the TDP-43 pathology.

For those who are having the "wait, what?" moment re TDP-43, I took the liberty of including brief excerpts of your helpful links (bolded areas are on me).

1.https://onlinelibrary.wiley.com/doi/abs/10.1111/ene.12706: TDP‐43 in amyotrophic lateral sclerosis – is it a prion disease?
Abstract
Amyotrophic lateral sclerosis is a devastating disease characterized by rapidly progressive paresis. The neuropathological hallmark of most amyotrophic lateral sclerosis cases are neuronal and glial aggregates of phosphorylated 43‐kDa TAR DNA‐binding protein (pTDP‐43). The accumulation of similar proteins...such as tau and amyloid‐β in Alzheimer's disease and α‐synuclein in Parkinson's show a stereotypical sequential distribution pattern with progressing disease. In this review, we discuss recent evidence that TDP‐43 in ALS may propagate similarly to other neurodegenerative disease proteins. We furthermore delineate similarities and important differences of TDP‐43 proteinopathies to prion diseases.
2. https://sci-hub.do/10.1111/j.1365-2990.2008.00963.x:Lack of TAR-DNA binding protein-43 (TDP-43) pathology in human prion diseases
Aims: TAR-DNA binding protein-43 (TDP-43) is the major ubiquitinated protein in the aggregates in frontotemporal dementia with ubiquitin-positive, tau-negative inclusions and motor neuron disease.... We therefore aimed to determine whether there is TDP-43 pathology in human prion diseases, which are characterised by variable deposition of prion protein (PrP) aggregates in the brain as amyloid plaques or more diffuse deposits... No abnormal TDP-43 inclusions were identified in any type of prion disease case... Conclusions: These data do not support a role for TDP-43 in prion disease pathogenesis and argue that TDP-43 inclusions define a distinct group of neurodegenerative disorders.
3.https://sci-hub.do/10.1016/j.celrep.2013.06.007: Prion-like Properties of Pathological TDP-43 Aggregates from Diseased Brains
TDP-43 is the major component protein of ubiquitin- positive inclusions in brains of patients with frontotemporal lobar degeneration (FTLD-TDP) or amyotrophic lateral sclerosis (ALS). Here, we report the characterization of prion-like properties of aggre- gated TDP-43 prepared from diseased brains... fragments of insoluble TDP-43... acted as seeds, inducing seed-dependent aggregation of TDP-43 in these cells.... One subtype of TDP-43 aggregate was resistant to boiling treatment...These results indicate that insoluble TDP-43 has prion-like properties that may play a role in the progression of TDP-43 proteinopathy.
4.https://sci-hub.do/10.1016/j.nbd.2016.08.007 In vitro prion-like behaviour of TDP-43 in ALS
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND), and 95% of familial and sporadic cases involve the deposition of insoluble aggregated, phosphorylated and cleaved TDP-43 protein. Accumulating clinical and biological evidence now indicates that ALS bears a number of similarities to the prion diseases, with TDP-43 acting as a misfolded ‘prion-like’ protein demonstrating similar underlying pathobiology. Here we systematically address the hypothesis that ALS is a prion-like disorder... These findings may guide therapeutic strategies in this rapidly progressive and invariably fatal disease.
In areas like vaccine safety, we can acknowledge wide divergence of views here, and still add to our collective wisdom on things related to Alzheimer's and ApoE 4!
Please share more of your expertise!
4/4 and still an optimist!

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Re: COVID-19 RNA Based Vaccines and the Risk of Prion Disease

Postby NoNotMe » Mon May 03, 2021 11:00 am

Hi Ben,

Welcome to apoe4.info. We are so grateful to our community for shedding light in so many diverse topics that relate to Alzheimer's Disease. I'm happy that Nancy was able to respond with her expertise in a way that expands the conversation for the good of our entire community. This is our strong suit, divergent view points that create a positive learning environment. Thank you for your contribution!

It seems like you have lots of information and we encourage you to continue to share your knowledge! Here is a link to Primer which was written by a doctor who is a member of our community who has 4:4 allele. She is a true inspiration! I'm also including the How To Guide as an encouragement for your active participation. Lastly, here is a link to the Search engine for further topics of interest.

We're very happy to welcome you to apoe4.info.

Best Regards,

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Re: COVID-19 RNA Based Vaccines and the Risk of Prion Disease

Postby floramaria » Mon May 03, 2021 11:21 am

benhadad wrote:For example, TDP-43 without any prompting from vaccines has been implicated in ALS.
As far as TDP-43 and its effects on disease, the research is all over the board. And while current research points to it being involved in prion-related diseases, the reason for this is not normally linked to anything in relationship to RNA vaccines pathway.
benhadad, for offering your insights on this subject. As someone who has had 2 doses of Moderna vaccine and found the original post on associated risk of prion disease from mRNA vaccines concerning, I have been following this thread. Your post eased my mind. Thank you.
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Re: COVID-19 RNA Based Vaccines and the Risk of Prion Disease

Postby DebbieG » Mon May 03, 2021 7:29 pm

Peter Attia interviewed Paul Offit today:

"Paul Offit is a pediatrician specializing in infectious diseases and an expert in virology and vaccine development. He currently serves on the FDA committee evaluating COVID-19 vaccines. In this episode, Paul’s second appearance on The Drive, he provides an update on all the SARS-CoV-2 vaccines currently deployed, explains why the concerns raised around the mRNA vaccines are not legitimate, and offers his view on the prospects and timeframe of reaching herd immunity...."

https://peterattiamd.com/pauloffit2/

I've only listened to part of it (so far, will definitely finish), but it seems like useful information for this conversation.


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