4 ms·

From what I got from skipping over the study, this isn't about beta-amyloid itself, but "triglyceride-rich lipoprotein" amyloid beta complexes. The amyloid bet

From what I got from skipping over the study, this isn't about beta-amyloid itself, but "triglyceride-rich lipoprotein" amyloid beta complexes. The amyloid beta plaques may be not cause, but symptom of the disease. Maybe the TRL-A-betas are causing the damage, get metabolized and after that the protein separates and then accumulates in the brain? The study states, the TRL-A-beta are causing inflammation, which they attribute for disease progression rather than A-beta plaque formation. > ...the findings presented in this study nonetheless support a now large body of evidence that demonstrates that the genesis of plaque is not the initiating trigger for neurodegenerative processes to be initiated, but rather, may be consequential. This study provides evidence that more subtle chronic interactive effects of peripheral metabolism of TRL-Aβ with the cerebrovasculature may be sufficient to potentially cause AD. So, clearing up A-betas may be just flushing the "damage logs".

ethbr0 5y ago
> This study provides, for the first time, direct evidence that hepatic expression of genes leading to the synthesis of human-Aβ is causally associated with corruption of the NVU, with cell death and brain atrophy realised. [...] Consistent with the hypothesis of increased neurovascular insult as a consequence of hepatic synthesis of TRL-Aβ, PET findings clearly demonstrated an age-associated increase in [Pittsburgh compound] uptake. We suggest that this was indicative of the marked abundance of amyloid-rich lipofuscin aggregates distributed within brain parenchyma and within vessel lumen. They definitely seem to lean into the neurovascular damage angle. I.e. liver produces amyloid-beta complexes, high levels of which result in neurovascular damage, resulting in lipids making it through and accreting in the brain. Which makes sense, as if your capillaries are less functional, how would you body clear plaques from a difficult to reach organ (the brain)?

ethbr0 5y ago

> This study provides, for the first time, direct evidence that hepatic expression of genes leading to the synthesis of human-Aβ is causally associated with corruption of the NVU, with cell death and brain atrophy realised. [...] Consistent with the hypothesis of increased neurovascular insult as a consequence of hepatic synthesis of TRL-Aβ, PET findings clearly demonstrated an age-associated increase in [Pittsburgh compound] uptake. We suggest that this was indicative of the marked abundance of amyloid-rich lipofuscin aggregates distributed within brain parenchyma and within vessel lumen. They definitely seem to lean into the neurovascular damage angle. I.e. liver produces amyloid-beta complexes, high levels of which result in neurovascular damage, resulting in lipids making it through and accreting in the brain. Which makes sense, as if your capillaries are less functional, how would you body clear plaques from a difficult to reach organ (the brain)?