Jaime Grutzendler

Truly beautiful myelin imaging Bobby, Congrats!!

Myelin–axon interface vulnerability in Alzheimer’s disease revealed by subcellular proteomics and imaging of human and mouse brain - Nature Neuroscience In Alzheimer’s disease (AD), disruptions in myelin and axonal structures occur, although the underlying mechanisms remain unclear. Here the authors show that, at the myelin–axon interface, axon–glial ...

At the myelin-axon interface, axon-glial signaling, paranodal architecture, and β-amyloid aggregation are altered in Alzheimer's disease, implicating myelin-axon disruption in disease progression

@jgrutzendler.bsky.social @yifeicai.bsky.social

www.nature.com/articles/s41...

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!

very appreciative of this collaboration!! @reimand.bsky.social

thank you Ethan, i hope all is well!

great, hopefully you enjoy it :)

Happy to share our latest publication on subcellular myelin proteomics and structural changes in Alzheimer disease www.nature.com/articles/s41...

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.

PLD3 affects axonal spheroids and network defects in Alzheimer’s disease - Nature Amyloid-plaque-associated axonal spheroids are prominent contributors to neural network dysfunction in an Alzheimer’s model and can be reversed by endolysosomal modulation.

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.

Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease - Nature Aging Axonal spheroids disrupt neural circuits in Alzheimer’s disease. In this study, using subcellular proximity labeling proteomics in human brain and iPSC modeling, the authors link spheroid formation to...

Happy to share our latest study, led by @YifeiCai_. We applied Antibody-Driven Proximity Labeling to analyze postmortem human brain tissue, mapping the molecular architecture of plaque-associated axonal spheroids (PAASs) in Alzheimer’s disease.

🔗 Read here: www.nature.com/articles/s43...

A petavoxel fragment of human cerebral cortex reconstructed at nanoscale resolution To fully understand how the human brain works, knowledge of its structure at high resolution is needed. Presented here is a computationally intensive reconstruction of the ultrastructure of a cubic mi...

www.science.org/doi/10.1126/...

Our lab at Yale U/Wu Tsai Institute has a postdoctoral position on neurodegeneration, neuro-glial-vascular biology using 2photon, calcium/voltage imaging, gene editing,transcriptome/proteome, 3D EM, translational neurosci/chemistry. Email me if interested. Forward to those interested pls

The future of Alzheimer's treatment A neurologist who studies Alzheimer’s disease says hopes are on the rise for new treatments that target tau proteins.

🧪Thanks to @rbaltman.bsky.social for having me on The Future of Everything podcast to talk about treatments for Alzheimer's disease. Give a listen if you're interested in an (anti)anti-amyloid antibody argument and some promising new drug targets. #Alzheimers
engineering.stanford.edu/news/future-...

interested!

Neuroscience methods - YouTube Nanocourse: Approaches to Study Neural Circuits This course was taught by Anita Autry, Tiago Gonçalves, and Luke Sjulson at Albert Einstein College of Medici...

Neuroscience students asked us to teach a PRACTICAL course on experimental methods, and it is now on YouTube!

Please like and repost to help us get the word out!

www.youtube.com/playlist?lis...

Lecture 1: Signals and data acquisition
Focusing on hardware, digital/analog I/O, synchronization
🧵

likewise, happy to have contributed to the comprehensive update on this important topic

I am delighted to share the work of my amazing student Dominic Isaacs! Out today in PNAS (www.pnas.org/doi/10.1073/...), Dom beautifully used optogenetics to show that thin-strand pericytes in the brain can send long-range electrical signals to control arteriole diameter and brain blood flow.

What a great initiative! 👉 Highlighting an outstanding paper by another researcher. 👉 Below is a must-read by @jgrutzendler.bsky.social and team 👇

www.science.org/doi/full/10....

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

Could one envision a synthetic receptor technology that is fully programmable, able to detect diverse extracellular antigens – both soluble and cell-attached – and convert that recognition into a wide range of intracellular responses, from gene expression and real-time fluorescence to modulation..

go.bsky.app/5Pz9Cp3

Transient upregulation of procaspase-3 during oligodendrocyte fate decisions Oligodendrocytes are generated throughout life and in neurodegenerative conditions from brain resident oligodendrocyte precursor cells (OPCs). The transition from OPC to oligodendrocyte involves a com...

elegant paper from Robert Hill’s lab

www.biorxiv.org/content/10.1...

In Vivo Optical Clearing of Mammalian Brain Established methods for imaging the living mammalian brain have, to date, taken the brain’s optical properties as fixed; we here demonstrate that it is possible to modify the optical properties of the...

www.biorxiv.org/content/10.1...

Super-resolution imaging of fast morphological dynamics of neurons in behaving animals - Nature Methods A variant of structured illumination microscopy called MLS-SIM allows super-resolution imaging of neuronal structures such as spinules, spines and boutons in awake mice.

www.nature.com/articles/s41...

A bistable inhibitory optoGPCR for multiplexed optogenetic control of neural circuits - Nature Methods PdCO is a switchable optogenetic tool for inhibiting synaptic transmission in neuronal terminals in vivo, as demonstrated in a variety of contexts mainly in the mouse.

interesting paper
www.nature.com/articles/s41...