Could AB still be the root cause of AD?

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mike
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Could AB still be the root cause of AD?

Post by mike »

Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer’s Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression

The researchers believe that AB is only dangerous when it is a soluble AB Oligomer. Soluble amyloid monomers and insoluble AB plaque are both non-toxic. You can have a lot of plaque and not have AD if you never get the soluble oligomer stage. They believe toxic AB oligomers cause neurons to die and Tau to form.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231952/
Abstract
A large body of clinical and nonclinical evidence supports the role of neurotoxic soluble beta amyloid (amyloid, Aβ) oligomers as upstream pathogenic drivers of Alzheimer’s disease (AD). Recent late-stage trials in AD that have evaluated agents targeting distinct species of Aβ provide compelling evidence that inhibition of Aβ oligomer toxicity represents an effective approach to slow or stop disease progression: (1) only agents that target soluble Aβ oligomers show clinical efficacy in AD patients; (2) clearance of amyloid plaque does not correlate with clinical improvements; (3) agents that predominantly target amyloid monomers or plaque failed to show clinical effects; and (4) in positive trials, efficacy is greater in carriers of the ε4 allele of apolipoprotein E (APOE4), who are known to have higher brain concentrations of Aβ oligomers. These trials also show that inhibiting Aβ neurotoxicity leads to a reduction in tau pathology, suggesting a pathogenic sequence of events where amyloid toxicity drives an increase in tau formation and deposition. The late-stage agents with positive clinical or biomarker data include four antibodies that engage Aβ oligomers (aducanumab, lecanemab, gantenerumab, and donanemab) and ALZ-801, an oral agent that fully blocks the formation of Aβ oligomers at the clinical dose.
Sonoma Mike
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shug
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Re: Could AB still be the root cause of AD?

Post by shug »

Thank you for this, Mike - I am scheduled for starting Donanemab study in two weeks (if I pass the screening) so am glad for this abstract and also the link to the other articles on the NIH site. Going to do some studying!
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laurie
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Re: Could AB still be the root cause of AD?

Post by laurie »

Beta Amyloid is a 'mediator' of aluminum causing Alzheimer's. People with ApoE4 produce more beta amyloid and aluminum makes this amyloid more toxic.

Mike, have you seen Tin Cups recent post in the prevention forum? If not, there is a book that I think you will be very interested in reading. Here is a link to the introduction of the book. There are active links in Tin Cup's post.
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https://prevent-alzheimers-autism-strok ... s-for.html


"I just read Dennis Crouse's 4th book, "Finding a Cause and Potential Cures for Alzheimer's Disease: Climbing the Ladder of AD".

In his first book he applied Bradford Hill’s criteria for causation. All nine principles were met for aluminum being a causal factor of Alzheimer’s. In his new book he applies causal inference from Pearl and MacKenzie ‘s book “The Book of Why” 2018. Causal inference is expressed in two languages: causal diagrams expressing assertions of causation based upon what we know and a symbolic mathematical language expressing what we want to know. By repeating this causal inference with different data sets, the ladder of causation can be climbed with each rung supporting the original assertion, expressed as the first rung, and thereby making it stronger.”

In this book he presents information on 15 biomarkers(hallmarks) which have been identified for diagnosing Alzheimer’s (for example beta amyloid, Tau, brain atrophy, glucose metabolism ……) to see if any of these could be a cause of Alzheimer’s. What he presents is every biomarker is a ‘mediator’ for aluminum causing Alzheimer’s. Here is the intro for the book. I should note the book is technical.

I think Dennis presents a strong case. I've been convinced for over 4 years (March 2018) such that I've been making my own "Silicade," high OSA (orthosilicic acid) drink per his recipe. My wife and I consume 3 cups/day each. In 2021, after drinking 4 cups high OSA water/day for 6 years, Dennis (at 76) and Laurie did a 24 hour urine collection test for aluminum and had levels of healthy 22 year olds. The test protocol is explained in the 4th book.

Dennis' wife Laurie is a member here and she moderates a FB group on his work. " by Tin Cup in Prevention Forum
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"True prevention is only possible by first discovering the cause of a disease such as Alzheimer's."
Dennis N Crouse
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