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?
The answers are a little complicated.
Join us for a brief journey through the history of Alzheimer’s research to understand why the amyloid hypothesis — the one that suggests targeting those plaques could treat the disease — proved so persistent in the face of almost constant disappointment.
We start with Alois Alzheimer’s turn-of-the-century discovery that such plaques were present in the brain of a woman with early-onset dementia. Then we cut to the 1990s, when the drug industry advanced its first big amyloid idea: a vaccine that would turn the body’s defenses against the offending plaque.
That, of course, would fail, just like the amyloid-directed pills and antibodies that followed. But, to many scientists, each sequential disappointment lit the way to a slightly better approach, one that might finally slow cognitive decline and result in a blockbuster drug.
Now, with the latest and arguably best amyloid-targeting therapy deemed a failure, the industry may at last be moving away from that approach to Alzheimer’s, having learned a series of hard lessons along the way.
Simply because . with in the current period of time . The Twenty First Century And So Called Modernity And Technology . We or should I state The Elites , Intellectuals . Noble Laurets .Scientists and others within the Health Care Industry are steeped in Politics , Self Agrandisement along with the reliance on Technology That it will works and create Miracles Of Untold Successes . A False Premise . It was only about twelve days ago one evening two friends and or associates and myself Trevor .A.Merchant were sitting at the Dunkin branch at 1752 Crosby Avenue in The Bronx , New York City . zip code . 10461 . where i have been a customer for nearly nineteen  years to drink coffee , read, write and within these three  attributes of excellence and ideals i would therein have other customers to communicate with , as knowledge is power and the sharing of knowledge truthfully is empowerment ,to quote ,unquote . So here it was that all three of us were debating and or addressing issues of fundamental , profound , importance and significance here in this nation and globally . during these debates . i for a million times spoke about how the people at that time in history were able to build The Brooklyn Bridge In The City Of New York which currently still stands Tall at one hundred forty  years and secondly another Icon and Supreme Structure . The Grand Central Terminal In The City Of New York , Within The Heart Of The Borough of Manhattan . This The main Centre Of The City Of The World . . Stands today . at one hundred four years  My points then and always were that The humans whom were responsible for the building of these two  icons and more were not privilege with technology then . rather they used their minds , brains .the love and enjoyment of work to so achieved these goals . So only on Friday . July . 26 . 2019 there was the magazine in the Wallgreens Rite Aid Store also on Crosby Avenue in The Bronx , 10461 .Titled The Builders . to quote ,unquote , there in this magazine the two  Master Pieces of Excellence as close as any one would attain to perfection historically inducted in this magazine as Hallmarks or land Marks . My conclusion here is that these current academia of all the categories are not able to come up with the majesty and beauty even with . Technology . The issue here with this major and critical illness is one clear result or example ., Samsung Electronics was to put their latest cell phone on the market nine fridays ago .the folding phone , they did not as it was not folding costing two thousands dollars each [$2,000] It is now reported that they will bring it to the market in the month of September , 2019 . i rest my case . thank you Trevor . . N.Y..C 4. 18 .p.m daylight savings times
We discuss why amyloid is correlated with Alzheimer not causative in a number of publications at the links below
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”
Or maybe amyloid is a downstream effect, and we need to look upstream for the culprit(s).
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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