4 ms·

I only have a passing understanding, so forgive me if I get some of this wrong, but my understanding is that the beta amyloid hypothesis is "disproven" from the

I only have a passing understanding, so forgive me if I get some of this wrong, but my understanding is that the beta amyloid hypothesis is "disproven" from the perspective that removing beta amyloid that has built up doesn't seem to resolve the symptoms. That is different than it isn't a causal link in the chain though. For example (making this up) I don't think we have disproven that beta amlyoid build-up causes inflammation, which actually causes the brain damage via a process that continues even once the beta amyloid is gone.

tux3 5y ago
What I find puzzling if the plaques are a link in the chain (as opposed to a symptom), isn't so much that beta-amyloid drugs stop short of outright resolving the symptoms, but that they don't seem to affect the progress of the disease. To continue with your example, if beta-amyloid was a major source of inflammation, and inflammation caused the damage, it'd seem reasonable to expect that removing the plaques would result in slowed cognitive decline. Strangely, this does not seem to happen in clinical trials.
randcraw 5y ago
As I recall, several studies have also shown that people can have high levels of amyloid-beta plaques (ABPs) in the brain and not show any signs of dementia. Between the two outcomes (ABPs exist but there's no decline, and ABPs are removed but dementia persists), the prevailing interpretation is that ABPs alone do not cause Alzheimer's. They seem to arise along with the cognitive loss, though not cause it. Tau deposits and associated neurofibrillary tangles have also been implicated in dementia, but also can be absent in those with the disease, so they too are not directly causal.
- catlikesshrimp 5y ago
  Everything you said is still consistent with the beta amyloid theory. The plaques don't cause dementia, they are supposed to lead to damage. Once dementia sets in, there is no turning back, the neuronal network has been damaged enough and you can't replace neurons (not most of them) Dementia is the main symptom of Alzheimer. And there are other causes of dementia, too.
- ABetaMale 5y ago
  The current most plausible perspective is amyloid-β pathology causes tau pathology which causes neurodegeneration. Thus it's not surprising that amyloid-β pathology can exist without neurodegeneration, if there is no tau pathology (or none yet). However, I have not heard of the opposite: people with cognitive decline and amyloid-β pathology but no tau pathology.

tux3 5y ago

What I find puzzling if the plaques are a link in the chain (as opposed to a symptom), isn't so much that beta-amyloid drugs stop short of outright resolving the symptoms, but that they don't seem to affect the progress of the disease. To continue with your example, if beta-amyloid was a major source of inflammation, and inflammation caused the damage, it'd seem reasonable to expect that removing the plaques would result in slowed cognitive decline. Strangely, this does not seem to happen in clinical trials.

randcraw 5y ago

As I recall, several studies have also shown that people can have high levels of amyloid-beta plaques (ABPs) in the brain and not show any signs of dementia. Between the two outcomes (ABPs exist but there's no decline, and ABPs are removed but dementia persists), the prevailing interpretation is that ABPs alone do not cause Alzheimer's. They seem to arise along with the cognitive loss, though not cause it. Tau deposits and associated neurofibrillary tangles have also been implicated in dementia, but also can be absent in those with the disease, so they too are not directly causal.

catlikesshrimp 5y ago
Everything you said is still consistent with the beta amyloid theory. The plaques don't cause dementia, they are supposed to lead to damage. Once dementia sets in, there is no turning back, the neuronal network has been damaged enough and you can't replace neurons (not most of them) Dementia is the main symptom of Alzheimer. And there are other causes of dementia, too.
ABetaMale 5y ago
The current most plausible perspective is amyloid-β pathology causes tau pathology which causes neurodegeneration. Thus it's not surprising that amyloid-β pathology can exist without neurodegeneration, if there is no tau pathology (or none yet). However, I have not heard of the opposite: people with cognitive decline and amyloid-β pathology but no tau pathology.