Hi Yifei, i gave full credit to you; this study would have not been possible without your fearless and collaborative approach!

Hi Yifei, i gave full credit to you; this study would have not been possible without your fearless and collaborative approach!

thank you Ethan, i hope all is well!

great, hopefully you enjoy it :)

thank Junjie!

We appreciate the contributions of our collaborators Angus Nairn, Kristen Brennand (@kristenbrennand.bsky.social), Evangelia Petsalaki (@e_petsalaki.bsky.social), and all coauthors.

#Alzheimers #Neuroscience #Proteomics #Neurodegeneration

To further investigate PAAS formation and modulation, we optimized an iPSC-derived AD model that develops spheroids closely resembling those in human brains. Inhibiting mTOR reduced PAAS pathology in cultures and in mice, suggesting that some axonal alterations in AD may be reversible.

Using proximity labeling proteomics, we identified abnormalities in protein turnover, cytoskeleton organization, and lipid transport, all linked to PI3K/AKT/mTOR pathway activation.

We previously showed that PAASs (dystrophic neurites) form in hundreds of axons around each amyloid plaque, blocking action potential conduction and disrupting neural circuits (www.nature.com/articles/s41...). However, their molecular composition remained unclear.

interested!

many thanks Eduardo for highlighting our paper. I agree, this is. great initiative!