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c618b9b695c4 | 4 years ago

I am in pharma, though not tied to Alzheimer's research.

A narrative of this-one-theory-being-kept-down-by-the-man is attractive, but a bit thin in practice. The amount we do not know about anything in biology (especially the brain) is staggering. Few researchers are willing to make definitive statements owing to our ignorance in the space. Biological research is the closest one can come to direct manifestation of Murphy's Law.

Many are invested in the amyloid hypothesis, but only because it is the most compelling target to date. Everyone knows the emperor has no clothes. If/when better evidence comes to light, the field would move accordingly. Until that time, pharma companies will keep throwing billions of dollars at abeta hoping that their compound will have an effect where others have failed.

Edit: corrected typo pointed out from below

discuss

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zzt123|4 years ago

When you say that the amount we do now know is staggering, do you mean the amount we do not know? The rest of your post suggests the latter, which is somewhat an antonym of what was actually written.

c618b9b695c4|4 years ago

Bah, yes that was a (now corrected) typo.

When speaking of biology, assume we know less than we think.

peddling-brink|4 years ago

> we do now know

I think should have been "we do not know"

btilly|4 years ago

You have argued for why we shouldn't be suppressing alternative hypotheses. But you haven't provided good evidence that this hasn't happened.

However a series of high profile articles and editorials have said that we have. For the latest example, read https://www.scientificamerican.com/article/alzheimers-inc-wh....

Given that, I will continue to believe that this area of science absolutely have acted in a non-scientific way.

Root_Denied|4 years ago

>If/when better evidence comes to light, the field would move accordingly.

This is a bit of an idealistic view.

It's entirely possible for large players within a given system to pick and choose winners, specifically in where they direct funding. This isn't the same thing as actively platforming against a particular path, just funding the one that they see as most promising.

I think the argument here revolves not around the "gerontologists hate this one trick that big pharma doesn't want you to know" but rather than there's some small number of people making decisions based on their own biases with regard to research directions and there's a dissenting group that would like to see broader research done before committing the finite available resources to just that one path.

tdeck|4 years ago

I remember a study from a few years ago that showed a compelling link between gum disease and Alzheimer's. What happened to that hypothesis? Has it gained any more traction?

ABetaMale|4 years ago

[1] is probably the study you're thinking of. There's also [2] regarding herpesviridae, among others.

In short, there are good reasons at this point to believe that amyloid-β's primary function is as antimicrobial peptide, and thus various infections may cause the seeding of amyloid-β deposits. These deposits may then persist for years beyond any useful benefit, especially if the brain's clearance mechanisms are impaired.

Note that, per [2]:

Importantly, in the antimicrobial protection model, neurodegeneration is not mediated by pathogen activities that directly kill neurons. Rather, Aβ innate immune pathways targeting pathogens mediate the AD [Alzheimer's Disease] neuropathogenesis that leads to widespread neurodegeneration. Thus, our model is consistent with the amyloid cascade hypothesis and overwhelming data showing the primacy of Aβ in AD pathology.

[1]. Dominy et al (2019). Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. https://doi.org/10.1126/sciadv.aau3333

[2]. Eimer et al (2018). Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection. https://doi.org/10.1016/j.neuron.2018.06.030

himinlomax|4 years ago

Note that tooth decay and gum disease are strongly linked to sugar consumption, high sugar consumption causes diabetes, and Alzheimer has been linked with type 2 diabetes. I don't know how popular this hypothesis is these days, but that's a possible link.