does brain connectivity drive spread of pathological proteins in Alzheimer’s disease?

✨ preprint: www.biorxiv.org/content/10.1...

if the question intrigues you, please read on 🧵⤵️

For more details, please check out the paper! A huge thanks to my coauthors @alaingoriely.bsky.social @jwvogel.bsky.social @alexapb.bsky.social @saadjbabdi.bsky.social @biofinder.bsky.social (and others not on Bluesky) for helping to get this over the line.

With help from Oskar Hansson, @jwvogel.bsky.social, @alexapb.bsky.social and the @biofinder.bsky.social team, we were also able to replicate this result in an independent dataset with a different tau tracer, the BF2 dataset!

We then fit the model to biomarker groups across the AD continuum in ADNI. Our results show an initial transport-dominated phase (A+T-), followed by a production-dominated phase (A+T+). Suggesting early cortical tau deposition via network diffusion is followed by accelerated local tau production.

We used a series of test/train splits on A+T+ ADNI subjects with at least 4 scans to show how adding data changes prediction uncertainty. We show that too few scans can lead to misleading predictions, but with 3 longitudinal scans, regional predictions are pretty good! (here showing left inf temp.)

Through model comparison on an A+T+ group from ADNI, using in-sample and out-of-sample measures, we show that regional heterogeneities are essential for longitudinal modelling of tau progression and highlight deficiencies in a network diffusion model and models with homogenous production dynamics.

First, we introduce a novel network reaction-diffusion model that uses regionally heterogeneous tau carrying capacities (the maximum amount of tau a region can hold), and show that the model reproduces tau spreading as observed through tau PET.

I'm thrilled that our paper "Personalised regional modelling predicts tau progression in the human brain" is finally published in PLoS Biology!

Here's a short thread about the main findings of the paper...

I am so very proud announce my lab's first preprint!!

@xiaoyucaly.bsky.social delves into the mechanisms driving tau distribution:
* Tau sequence driven by connectivity dynamics
* Tau load driven by local factors

Check out her thread below

🧠New preprint! What drives tau, the pathological protein in AD, to spread?
We found that WHERE tau appears and HOW MUCH accumulates are governed by different mechanisms. Check it out:
www.biorxiv.org/content/10.1...


#MedSky #neuroskyence #neurosky #alzsky #compneuro #MRI #neuroimaging #neurology

🚨REVIEW
We have written a review on the emerging topic of nonequilibrium, irreversible dynamics in the brain.

Now out on the arXiv: arxiv.org/abs/2504.12188

We introduce the relevant mathematical frameworks, discuss recent interesting results, and look to the future of this research direction!

Modelling cerebrovascular pathology and the spread of amyloid beta in Alzheimer’s disease: royalsocietypublishing.org/doi/10.1098/... #ProcA #Alzheimers #biophysics

In this paper, we connect local damage to brain vasculature to global progression of toxic proteins leading to neurodegenerative diseases.
royalsocietypublishing.org/doi/epdf/10....
We identify situations where disease initiation can be caused by focal hypoperfusion following vascular injury.

🚨PERSPECTIVE

We have written a perspective calling for a holistic approach to mathematical modelling for biological systems - it now out on the arXiv: arxiv.org/abs/2503.20511

A thread 🧵

🚨 NEW PAPER ALERT!

After such a long journey, I am so glad to see this published in
@PNASNews:

pnas.org/doi/10.1073/...

Big thanks to @leonardobonetti.bsky.social, Gemma Fernandez-Rubio, Peter Vuust, Gustavo Deco, Morten Kringelbach, Renaud Lambiotte and @alaingoriely.bsky.social

A thread...

Why academia is sleepwalking into self-destruction. My editorial @brain1878.bsky.social If you agree with the sentiments please repost. It's important for all our sakes to stop the madness
academic.oup.com/brain/articl...