We were unable to find support for the claim that lecanemab binds a different, more soluble, human target than aducanumab and donanemab. Antibody preference for plaques vs CAA is unlikely to explain differences in ARIA-E rates. alz-journals.onlinelibrary.wiley.com/doi/10.1002/...
Do we grow wiser as we age?
I spent 15+ years chasing glam journals, wasting time and energy (and frustrating my team and co-authors).
I don’t want to wake up at 70 and realize my life went into convincing a few editors my work was trendy enough.
Enough. I’ll try to be smarter.
My favorite NIH entity is the Council of Councils, which sounds like it might launch a war to defend Naboo.
Knowing little about this, I’d ask how complex matrix C (the FC map) is - how many baseline circuits and regions there are. If it’s only a few highly connected regions in few circuits (eg the DMN), then I see their point. If the # of circuits >> # patients and lesions, then LNM should be valid?
Graph titled "Paying for Impact 2025" showing Article Processing Charge (APC) vs Impact Factor for a selection of top journals in neuroscience - linear trendline R^2=0.636
Updating this graph for the holidays 🎁
(datapoints are a selection of journals publishing in neuroscience)
Introducing Nature Baubles, the latest addition to Nature Portfolio. open.substack.com/pub/andrewms...
Updates to the submission process for LOIs and grants requesting more than $500K in any budget periods. grants.nih.gov/grants/guide...
Hi Usha, I would be happy to discuss the misinformed narrative about the Alzheimer’s field Piller is pushing. And perhaps you or he can explain why my ongoing work and that of thousands of others is part of a “Devastating Legacy of Lies.”
I fully agree. The term LLPS is probably not the correct one to describe what happens in cells.
However, the formation of dynamic low-order condensates driven by low affinity multivalent proteins (often highly disordered) seems to occur in cells.
If not LLPS, what term would you use to describe these quick off-rate polyvalent structures that show rapid FRAP recovery, droplet-mixing, etc? QuORPS?
Well I see the appeal of using “liquid” as a term to describe a collection of polyvalent interactors, sliding along one another through rapid associations and dissociations. What would be a better term for this, distinct from aggregates with irreversible monovalent (oligovalent?) interactions?
Do you think it better to describe condensates as concentrations of disordered macromolecules with specific but polyvalent interactions and quick off-rates?
Any cryoEM folks know what these strange zebra-stripe particles are in a prep from human brain?
We are looking to hire a postdoc to take this and other TDP-43 assay development forward! Please re-post!
Our study “Genetic and proteomic analysis identifies BAG3 as an amyloid‑responsive regulator of neuronal proteostasis" was published in Acta Neuropathologica this week! Congratulations to lead author Zach Augur, who will be defending his thesis later this week!!
link.springer.com/epdf/10.1007...
Working with David Walt’s lab, here is a new tool we hope to develop into a diagnostic test for TDP-43 pathology, something we desperately need in cognitive neurology. www.medrxiv.org/content/10.1...
My lab is hiring a postdoc to work on new TDP-43 biomarkers! Please get in touch and re-post!
BREAKING: Field makes inchwise progress over decades on intractable problem of dementia with interesting leads and blind alleys but smart people are doing their best and please don’t overinterpret their results because it takes a long time for a real breakthrough
www.bostonglobe.com/2025/08/06/m...
First highlight...
Senator Capito started of the discussion saying that the bill contains AN INCREASE for NIH.
The details are not available, but the bill will be released ofter the hearing.
This is not a done-deal, but it does show where the Senate is on a bipartisan basis.
My lab is hiring a postdoc to work on new TDP-43 biomarkers! Please get in touch and re-post!
New TYP lab publication led by PhD student @alexlish.bsky.social out today in @cp-cellreports.bsky.social! We present a reproducible neuron-astrocyte-microglia tri-culture model to better reproduce intercellular interactions in Alzheimer's disease. Read more here: www.cell.com/cell-reports...
Well said!
Thanks guys. To be clear, I still favor that antibody directly binding to CAA could be a cause of ARIA. We just found that the difference in ARIA-E between lec and adu can’t be fully explained by differences in CAA preference.
We studied the binding of clinical antibodies to human brain extracts and found no evidence that lecanemab binds a more soluble population of Abeta than aducanumab or donanemab, nor that binding preferences to CAA vs plaque explained different ARIA rates. www.biorxiv.org/content/10.1...
Thrilled to share my first first-author paper is out
@cp-neuron.bsky.social! We show that Alzheimer's disease protective CLU alleles upregulate CLU in response to neuropathology, dampening inflammatory signaling between microglia and astrocytes.
Read here www.sciencedirect.com/science/arti...
Congratulations our newly-minted PhD candidate Olivia Pembridge on passing her PQE with flying colors today! Olivia will be using a wide array of iPSC and organoid models to study mechanisms of neurodevelopment!
