Wilfried Rossoll
rossolllab.bsky.social
Wilfried Rossoll
@rossolllab.bsky.social
Translational Neuroproteomics Lab | Understanding mechanisms of protein (dis)aggregation in neurodegenerative diseases | Views = own
Our study provides a first comprehensive overview of pTau-associated proteomes across tauopathies and uncovered several important findings. It is also a starting point for further ongoing ProPPr projects, where will put everything that we have learned during this long journey to good use.
March 13, 2025 at 11:14 PM
Our further analysis demonstrated that infiltration of astrocytic plaques with FTL-positive microglia is a characteristic feature of CBD pathology. The observed complex co-localization patterns underscore the importance of using fluorescence microscopy to follow up on proximity proteomics findings.
March 13, 2025 at 11:11 PM
To discover proteins with differential association with pTau lesions between AD, CBD, PiD and PSP, we performed statistical comparison of protein abundances with MiST. We found a strong pTau-association of ferritin light chain (FTL) for CBD but this did not identify cell types or pTau lesions.
March 13, 2025 at 11:09 PM
We then selected a set of common or tauopathy-specific enriched proteins for further analysis with immunofluorescence and quantitative analysis. Represented in all tauopathies was the core retromer complex protein VPS35 that we found sequestered in several types of pTau lesions in all tauopathies.
March 13, 2025 at 11:06 PM
We used AT8 phospho-tau (pTau) antibody as a probe to determine the composition of disease-specific pTau-associated proteomes in post-mortem frontal cortices of four major tauopathies in situ. We report 1,317 pTau associated proteins, with 409 being new, showing concordance with previous efforts.
March 13, 2025 at 11:04 PM
To identify proteins that associate with tau pathology in these tauopathies, we developed an approach for in situ proximity labeling and isolation of aggregate-associated proteins using glass slides with standard 5μm thin formalin-fixed paraffin-embedded (FFPE) human brain tissue, termed ProPPr.
March 13, 2025 at 11:00 PM
Here we addressed the great disease-specific morphologic and biochemical diversity of tau aggregates in Alzheimer’s disease (AD), corticobasal degeneration (CBD), Pick’s disease (PiD), and progressive supranuclear palsy (PSP), that remained to be explored with unbiased methods such as LC-MS/MS.
March 13, 2025 at 10:58 PM