Andrew Stern

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!

Astrocyte induction of disease-associated microglia is suppressed by acute exposure to fAD neurons in human iPSC triple cultures Lish et al. present a co-culture system of iPSC-derived human microglia, astrocytes, and neurons to investigate intercellular communication across different environmental and genetic contexts. Transcr...

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.

Anti-amyloid antibody equilibrium binding to Aβ aggregates from human Alzheimer disease brain Importance: Anti-amyloid immunotherapy is used to treat Alzheimer disease (AD) with moderate benefits and potentially serious side effects due to amyloid related imaging abnormality with effusions/ede...

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...

CLU alleviates Alzheimer’s disease-relevant processes by modulating astrocyte reactivity and microglia-dependent synaptic density Genetic studies implicate clusterin (CLU) in the pathogenesis of Alzheimer’s disease (AD), yet its precise molecular impact remains unclear. Through u…

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...

Oh! It was finally approved today! 🍾🍾

ec.europa.eu/newsroom/san...

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!

If you're headed to #ADPD next week, be sure to stop by the TYP lab presentations by @gizemterzioglu.bsky.social and Zach Augur to learn about some of the amazing work the lab is doing!

Zach Augur will be presenting a poster during Shift 1 on April 2nd and 3rd titled "BAG3 IN ALZHEIMER’S DISEASE AND ITS IMPACT ON ASTROCYTE FUNCTION AND DISEASE PROGRESSION"

@gizemterzioglu.bsky.social will be presenting at the Microglia Symposium on the afternoon of April 4th! Her talk is titled "INPP5D/SHIP1 REGULATES MICROGLIA FUNCTION AND INFLAMMATORY RESPONSE IN ALZHEIMER'S DISEASE"

Yes SEC followed by several techniques like ELISA, Western blot, EM, etc.

It’s good to be skeptical! I agree - I don’t think there’s a distinct atomic structure of oligomers/protofibrils as distinct from fibrils found in plaques. But there are reasons “they” said these things.

We’re still working on it! We have some interesting SEC data to share with you. I think Dennis or our postdoc Youqi will present some at AD/PD if you’ll be there (I won’t).

Amyloid-β oligomerization in Alzheimer dementia versus high-pathology controls - PubMed The results raise the intriguing hypothesis that the linkage between plaques and oligomers may be a key pathophysiological event underlying dementia of the Alzheimer type. This Aβ oligomer assay may b...

The homogenization, centrifuge speeds, detection methods, etc always vary paper to paper but the finding is reproducible. See also eg pubmed.ncbi.nlm.nih.gov/23225543/

Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease Genetic evidence strongly supports the view that Aβ amyloid production is central to the cause of Alzheimer's disease. The kinetics, compartmentation, and form of Aβ and its temporal relation to the ...

In the case of Abeta, also from observations that aqueously extracted aggregates correlate with disease better than plaques do, but without structural information about those aggregates other than some antibody binding studies. Eg onlinelibrary.wiley.com/doi/abs/10.1...

A very thoughtful and sobering piece by Dr. Jason Karlawish.

"The problem is that the facts don't support Piller's message. It's sensational, and in my experience, it's causing harm."

How a Book Is Undermining Progress Against Alzheimer's www.medpagetoday.com/opinion/seco...

It was distressing to see the skepticism about Alzheimer's disease research expressed at the Bhattahcharya hearing today.

This has been fueled by Charles Piller's sensationalized (NOT sensational) reporting and book.

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There is no ‘amyloid cabal’ in Alzheimer’s research “There exists no ‘amyloid cabal’” in Alzheimer’s research, neurologist Dennis Selkoe writes in response to Charles Piller’s “Doctored.”

Many Alzheimer’s researchers are also unhappy with Piller’s recent book and its negative characterization of the field, in which he inflates the significance of isolated fraud cases to argue that the entire field is corrupt. Here’s a rebuttal from my colleague Dennis Selkoe, published in STAT News:

Baldwin Blasts Trump Administration for Stopping $65 Million for Alzheimer’s Disease Research | U.S. Senator Tammy Baldwin of Wisconsin WASHINGTON, D.C. – Today, U.S. Senator Tammy Baldwin (D-WI), Ranking Member of the Senate...

@baldwin.senate.gov released a press release calling out the administration for damaging the Alzheimer's Disease Research Center network through it's screwing up NIH processes.

www.baldwin.senate.gov/news/press-r...

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If you want to learn about Charlie Piller's journalistic integrity, read this (long) thread.

bsky.app/profile/jere...

It is pretty telling...sensationalism without regard to getting the facts right.

Congratulations to the newly minted PhD @alexlish.bsky.social on successfully defending her thesis today! Be on the lookout for all the amazing things to come from Dr. Lish!

(To the tune of My Sharona)

CNS’s macrophage
Myeloid fate
Can disease-associate
Microglia!

RNA xkcd.com/3056

And reviewers requiring grant applicants to fit theories and proposals to data does not make them a cabal! All theories of AD must still account for observations like APP and PSEN mutations even if they focus on infections or inflammation or whatever - otherwise they are bad theories.

Agreed. There’s no mafia (or maybe I just haven’t been “made” with a cigar behind the tissue culture hood). We can’t go around calling everyone trying to fit their models to the data a fraudster, even if there are some out there. And you’re right we need all the data we can to fit our models to.

I appreciate your good-faith attempt at calculating a real amyloid clearance effect. But this is not Piller’s goal. He seems to want to call researchers who simply make strong predictions on strong observations (APP and PSEN mutations cause AD!) fraudsters and mafiosos in order to sell his book.

@sjorsscheres.bsky.social

Some thoughts on “protofibrils.” www.alzforum.org/news/researc...