The idea that sticky brain plaques cause Alzheimer’s disease began as an interesting hypothesis and eventually became drug industry dogma. Now, after a string of clinical trial failures, that hypothesis looks less credible than ever.

But how did nearly two decades of failure not convince the brightest minds in pharma that it was time to move on?

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  • Most adults are incapable of coming to terms with an idea that does not fit their beliefs.
    Therefore, i think that Altzheimers is the endResult of habitual cynicism and denial.

    The precedent of senility is in our mental habit of dismissing dissonant information.
    As this cognitive squeamishness progresses through a lifetime of selective blindness,
    the stupids become what they do : they become their dishonest mental habits.
    Meanwhile perceptiveness and curiosity attrophies until the deniers become dysfunctionally stupid.
    Stupidity has a trajectory !

    We know that yoga and psychotropics affect brain structure :
    so it is reasonable to predict that wilfulStupidity also affects brain structure.

    This i know, because i have been an innovator all my life (68years) :
    Most people dismiss me (and other accomplished thinkers) as not-worth-understanding,
    in preference to doing the cognitive work of making sense of a different perspective.

    Hence Altzheimers is the destination of choice for most of my contemporaries.
    This applies irrespective of whether one starts out smart or dull :
    Only by facing the unknown with intrepid discernment can we stave off the inertia of accumulatingStupidity.

    In this context, belief is our worst enemy : because belief automatically dismisses dissent.
    Whether it comes from another individual or one’s own perceptions,
    people are in the habit of making the world conform to their beliefs/disbeliefs.

    And perhaps worst of all, belief is the counterfeit of knowledge.
    Only understandings which are personally empirically verified can be trusted.

  • I have enjoyed reading the stimulating comments, and only write to thank Damian G for a very well done and pithy history, nice work!

  • Look up the work of Dale Bredesen, M.D. he is a neurologist who is/was at UCLA, and now has the Buck clinic in the LA area. He has identified 36 deficits in Alzheimer’s disease, which suggests that there is not going to be any single drug to treat this increasing common and devastating illness. As a retired physician who had both parents die with dementia, to say that I’ve been reading all I can find , is a gross understatement. ApoE4 positive also. He looks at all aspects of a persons life, and addresses them all. There are specific supplements, including vitamin deficiencies that are addressed. Also exercise, nutrition, and even meditation. He trains physicians in what he and his lab cohorts have learned and his work with patients is encouraging. He has written a book, “ The End of Alzheimer’s”, which is for lay people who may not be able to find a physician familiar with his work. I gave my doc a copy of the book last year. He and his colleagues have also written articles that appear in the scientific literature.

  • Alzheimer never suggested plaques and tangles were the cause of dementia. Indeed, this is what he wrote in 1911: “So scheint wirklich kein stichhaltiger Grind vorhanden, diese Fälle als durch einenbesonderen Krankheitzprozeβ verursacht zu betrachten” . “There is then no tenable reason to consider these cases as caused by a specific disease process”

  • The classic term “multiple ways lead to Rome” seems to have been lost in the funding preferences for amyloid-only research for Alzheimers. Hopefully now the blinders come off – also in funding allocation for many other diseases.

  • The problem is if not amyloid hypothesis, what is it? So far, that theory is still the one supported by the most empirical evidence from basic research. Do rodents have different pathologies than human? Maybe. Have scientists overlook other possibilities? Maybe. All in all, we are back to scratch if the amyloid hypothesis turns out to be false.

    • The only reason amyloid has all the data is because everybody else’s great non-amyloid ideas were not funded. You know why? Because EVERYONE knew it was amyloid. There are plenty of other quite plausible ideas, you only need to look.

    • The evidence for the causative role of cholesterol in heart disease also came from early onset familial genetics leading to hypercholesterolemia. And, the APOE4 variant, which is a genetic to sk factor in 60% of all Alzheimer’s patients leads to excessive amyloid deposition. A mutation in the amyloid precursor protein, which precludes amyloid formation protects against Alzheimer’s in the presence of APOE4. Two mutations causing late onset Alzheimer’s are in the gene ADAM10, which normally preclude amyloid formation.
      So, genetic studies show that amyloid causes this disease. Meanwhile, brain imaging studies shows amyloid does so 10 or more years before symptoms. This is why anti-amyloid therapies fail in people who already have symptoms of Alzheimer’s.
      Let’s move on and develop anti-amyloid treatments for early prevention of Alzheimer’s in people with brain amyloid, but no symptoms using early detection-early intervention. Meanwhile, we need to treat Alzheimer’s patients who already have symptoms with therapies that stop neuroinflammation.

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