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Taken out of context, the press release makes this finding look a lot more ground-breaking than it is after I quickly read through the actual study. Still a good piece of work though.

It was already known, as pointed out in the actual paper, that Amyloid-beta (AB) and Tau, the proteins that have long been implicated in Alzheimer's disease (AD), have prion-like properties which means they exist in an abnormal 3D configuration that causes other AB/tau proteins they interact with to adopt this abnormal configuration.

But they can also polymerize into large neurofibrillary tangles (NFTs). Patients who died late, e.g. at age 80 with AD had a lot of these NFTs, so it seemed reasonable by many to assume that these NFTs are the major cause of brain deterioration. But there were a number of alternative hypotheses of what exactly AB and tau were doing in the disease.

This study suggests that AB and tau cause disease primarily through their prion-like activity and not due to their ability to accumulate into large trash-balls (NFTs). They noted that patients who died young of AD had very few NFTs but have a lot of the AB/tau prion-like forms, whereas patients who survived longer had a lot of NFTs but not a lot of prion activity. This lends evidence to the idea that the primary pathogenicity of AB/tau is through their prion activity and not the fact that they accumulate into large protein blobs.

The big issue that AB/hyperTau studies seem to studiously ignore: studies in human brains have found an inverse correlation between the sites of the brain with excess plaque formation and the sites of the brain with the most significant atrophy and functional decline.

This is unsurprising, given the last two decades of drug trials targeting these molecules have all uniformly failed.

The alternative hypothesis is that these plaques are protective against neuronal infections that provoke alzheimers. That hypothesis has not garnered wide support yet, though it is growing, and is at least consistent with the inverse relationship observed.

could that be interpreted as the ones with trash balls (NFTs) might actually be the ones handling it 'better'?

You mean like the NFTs are somehow protective against the Prion forms? That is a possible interpretation that this study does not directly disambiguate.

Could just be an innocuous buildup with no effects either way, that just results from having the disease a long time. I doubt it's a direct result of handling the disease well but I don't know anything about what defenses our brains have against prions

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