Out now in Brain: Our new study shows that tau deposits in Alzheimer’s disease not affect gray matter but also drive degeneration of connected white matter tracts, offering mechanistic insight into how tau disrupts brain networks
academic.oup.com/brain/articl...

Very happy to share our 2nd paper today, led by Lukas Frontzkowski: We developed a novel data driven reference region for PI-2620 PET tailored to assess 4R tauopathies, improving i) PSP vs. control separation and ii) PET associations with clinical scores
doi.org/10.1007/s002...

Happy to share our new work by Carla Palleis in Movement Disorders showing that brain networks shape neurodegeneration patterns in PSP
=> This suggests that grey matter atrophy expands across connected brain regions, potentially following tau accumulation in PSP

doi.org/10.1002/mds....

4/Next, we tested whether Aβ-induced hyperconnectivity promotes tau spread. Supporting this, we found that hyperconnectivity of tau epicenters was linked to faster tau spread across connected regions, mediating the effects of Aβ on tau spread

3/We then tested whether Aβ as measured via amyloid-PET induces hyperconnectivity in AD patients. Indeed, we found that Aβ is linked to fMRI-based connectivity increases in patients across the AD spectrum consistent across ADNI and A4 samples

2/To test this, we used subject-level resting-state fMRI to determine connectivity of tau epicenters in AD patients from ADNI and A4 participants

4/Next, we tested whether Aβ-induced hyperconnectivity promotes tau spread. Supporting this, we found that hyperconnectivity of tau epicenters was linked to faster tau spread across connected regions, mediating the effects of Aβ on tau spread

Happy to share our new preprint led by Johannes Gnörich and @matthiasbrendel.bsky.social, showcasing a full ATN staging approach using a single dynamic PI-2620 scan, leveraging advanced kinetic modelling techniques

www.medrxiv.org/content/10.1...

Happy to share our new work led by Johannes Gnörich and Matthias Brendel, suggesting a visual read algorithm for PI-2620 in 4R taupathies. Early imaging windows, kinetic modelling and basal ganglia are key!

doi.org/10.1016/j.ne...

Paper alert: We performed a prognostic validation of the MDS PSP criteria, showing most patients with possible/suggestive PSP show an increase in diagnostic certainty over time. Increase in diagnostic certainty could be used as an endpoint in trials
doi.org/10.1002/mds....

5) Tau sits primarily at grey/white matter boundary zones in PSP. Targeted PET assessment at the GM/WM boundary can help tease out group PSP vs. control differences

4) In PSP patients, PI-2620 captures primarily neuronal/oligodendroglial tau

3) PET to autopsy correlation shows good correspondence between in vivo PI-2620 imaging and post-mortem tau assessments in PSP patients

2) Post-PET imaging cell-sorting in 4R mice confirms that PI-2620 is stuck in neurons not in astrocytes

1) PI-2620 captures tau accumulation in a 4R tauopathy mouse model