William A. McEwan

Templated seeding induces the formation of Alzheimer paired helical tau filaments in human brain organoids

Cortical organoids from healthy human iPSCs, seeded with Alzheimer brain tau, form three-repeat tau filaments that cryo-EM shows are identical to Alzheimer paired helical filaments and need endogenous tau.

Templated paired helical filament formation and tau fold-dependent inclusion morphologies in primary neurons

This study shows that primary neurons can propagate Alzheimer's disease paired helical filaments and that tau filament folds determine inclusion morphologies.

Tracking tau and cellular responses in human iPSC-microglia from uptake to seedable secretion in extracellular vesicles

This study shows human iPSC-derived microglia uptake and process tau fibrils, leading to secretion in extracellular vesicles that can seed tau aggregation in neurons.

Small tau aggregates exhibit disease-specific molecular profiles across tauopathies

The paper identifies disease-specific molecular profiles of small tau aggregates across different tauopathies using single-molecule assays.

Neurodegeneration emerges at a cellular tipping point between aggregate accumulation and removal.

The paper identifies a cellular tipping point between aggregate accumulation and removal as a universal feature of neurodegeneration, validated through live-cell assays and super-resolution imaging.

Sensitive detection and propagation of brain-derived tau assemblies in HEK293 based wild-type tau seeding assays

This study develops a biosensor assay to detect and propagate brain-derived tau assemblies using full-length, wild-type tau in HEK293 cells, showing it can replicate disease-relevant phosphorylation and seeding properties.

SynPull: a novel method for studying neurodegeneration-related aggregates in synaptosomes using super-resolution microscopy

SynPull combines single-molecule pulldown, super-resolution microscopy, and computational analysis to study protein aggregates in synaptosomes from human and mouse samples, revealing AT8-positive tau as the predominant aggregate in Alzheimer's disease.

Antibody-dependent Intracellular neutralisation by TRIM21 is potentiated by HOIP and linear ubiquitin chains

This study identifies HOIP and linear ubiquitin chains as critical for TRIM21-mediated ADIN by recruiting VCP, enhancing virus neutralization.

Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue

The paper investigates whether tau assemblies behave like independently acting prion-like particles in mouse neural tissue and finds that seeding behavior only occurs at supra-physiological concentrations.

Microglia become hypofunctional and release metalloproteases and tau seeds after phagocytosing live neurons with P301S tau aggregates

The paper shows that microglia phagocytosing neurons with tau aggregates become hypofunctional and release tau seeds, contributing to tauopathy progression.

Substrate-induced clustering activates Trim-Away of pathogens and proteins

This study reveals how substrate-induced clustering activates TRIM21's ubiquitination activity for antiviral responses and protein degradation, introducing optogenetically controllable TRIM21-nanobody chimeras.

Learning to count: determining the stoichiometry of bio-molecular complexes using fluorescence microscopy and statistical modelling

This paper introduces a method combining fluorescence microscopy and statistical modeling to accurately determine the stoichiometry of bio-molecular complexes.

Disassembly of Tau fibrils by the human Hsp70 disaggregation machinery generates small seeding-competent species

This study shows that the Hsp70 disaggregation machinery disassembles Tau fibrils, generating small seeding-competent Tau species that can drive aggregation.