[c618b9b695c4]

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

[zzt123]

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]

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

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

[peddling-brink]

> we do now know

I think should have been "we do not know"

[btilly]

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]

>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]

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]

[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

[tdeck]

This is such a great reply, thank you!

[himinlomax]

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.

[luigibosco]

Diabetes and Alzheimer's Disease: Mechanisms and Nutritional Aspects: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209735/

While it may be considered andectoal, this fits with what i've seen in my family. In my mind and from what i've read it seems to be more of a combination of factors - diabetes, an APOE gene, toss in a little depression/loss of purpose/retirement/isolation, etc

I find the studies with gamma interesting: https://www.alzheimers.gov/clinical-trials/gamma-induction-a...

I think it would be good to bring more attention to noticing when things start to slip, because as things progress there can be less openess to trying new things/focus on maintaining state.