Sjors H. W. Scheres

Oligodendrocytes may provide the extra density of α-synuclein filaments from multiple system atrophy

The paper investigates how oligodendrocytes contribute to the formation of α-synuclein filaments in multiple system atrophy by comparing seeded aggregation in different cell types.

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.

Prion-like transmission of human tau strains in the mouse brain

This study demonstrates that tau filaments from Alzheimer's and corticobasal degeneration patients can seed the formation of structurally identical mouse tau filaments, supporting the prion-like transmission hypothesis.

De novo design of flexible protein interactions with GuideFlip

GuideFlip co-designs protein structure and sequence for flexible targets, improving in silico success rates and experimentally validating binders to disordered proteins.

The Pick fold in tau filaments from human MAPT mutants

This study reports cryo-EM structures of tau filaments from MAPT mutants, showing how specific mutations alter the Pick fold structure and enable reconstitution of variants.

The amyloid packing difference: a pairwise comparison metric for amyloid structures

The paper introduces the amyloid packing difference (APD) metric to quantify differences between amyloid structures and demonstrates its application across various proteins and diseases.

Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments

This study identifies twelve phosphomimetic mutations in tau that induce the formation of paired helical filaments in vitro, mimicking Alzheimer's disease structures.

Dimerisation and twist reversal of the Lewy fold in α-synuclein mutants with Parkinson's disease and dementia

The paper reports the structures of α-synuclein filaments from individuals with Parkinson's disease and dementia, revealing differences in dimerisation and twist reversal between pathogenic and non-pathogenic variants.

Cryo-EM image processing of amyloid filaments in RELION-5.1

The paper introduces new tools in RELION-5.1 for automated processing and analysis of cryo-EM images of amyloid filaments, demonstrating their application on experimental datasets.

Seed structure and phosphorylation in the fuzzy coat impact tau seeding competency

This study shows that tau filament seeding capacity depends on both core structure and phosphorylation in the fuzzy coat, with phospho-mimetic residues restoring activity in modified tau.

Serial amplification of tau filaments using Alzheimer's brain homogenates and C322A or C322S recombinant tau

This study investigates tau filament assembly using mutant recombinant tau and brain homogenates, finding that specific mutations produce filaments resembling AD pathology.

Novel tau filament folds in individuals with MAPT mutations P301L and P301T

The paper reports cryo-EM structures of tau filaments from individuals with P301L and P301T MAPT mutations, revealing distinct filament folds associated with FTDP-17.

Cryo-EM structure of the vault from human brain reveals symmetry mismatch at its caps

The paper presents the cryo-EM structure of vault particles from human brain tissue, revealing a symmetry mismatch at their caps and its implications for therapeutic modifications.

Tau filaments with the Alzheimer fold in cases with MAPT mutations V337M and R406W

The paper determines the structures of tau filaments in individuals with MAPT mutations V337M and R406W using cryo-EM, finding the Alzheimer fold in all cases and a new triple filament assembly.

An image processing pipeline for electron cryo-tomography in RELION-5

The paper introduces an image processing pipeline for electron cryo-tomography in RELION-5, enabling automated atomic model building from tomographic data.

TAU FILAMENTS WITH THE CHRONIC TRAUMATIC ENCEPHALOPATHY FOLD IN A CASE OF VACUOLAR TAUOPATHY WITH VCP MUTATION D395G

The paper reports that tau filaments in vacuolar tauopathy with VCP mutation D395G have the CTE fold, similar to environmentally induced diseases.

Automated model building and protein identification in cryo-EM maps

ModelAngelo combines convolutional and graph neural networks with protein language model embeddings and hidden Markov model searches to automate atomic model building and identify unknown proteins in cryo-EM maps.

Cryo-EM structures of Aβ40 filaments from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy

The paper determines cryo-EM structures of Aβ40 filaments from Alzheimer's and cerebral amyloid angiopathy samples, revealing structural differences at higher resolution.

Cryo-EM structures of Tau filaments from the brains of mice transgenic for human mutant P301S Tau

The paper determines cryo-EM structures of Tau filaments from transgenic mice models and identifies differences compared to human Tau filaments.

Cryo-EM structures of tau filaments from SH-SY5Y cells seeded with brain extracts from cases of Alzheimer's disease and corticobasal degeneration

The paper reports cryo-EM structures of tau filaments formed in SH-SY5Y cells seeded with brain extracts from Alzheimer's and corticobasal degeneration cases, showing some structural templating.

Cryo-EM structures of chronic traumatic encephalopathy tau filaments with PET ligand flortaucipir

The paper uses cryo-EM to study tau filaments from Alzheimer's and CTE cases with and without flortaucipir, finding binding only in CTE Type I filaments.

Abundant Aβ fibrils in ultracentrifugal supernatants of aqueous extracts from Alzheimer's disease brains

The paper reports the presence of abundant Aβ fibrils in aqueous extracts from Alzheimer's disease brains, with structures identical to those in amyloid plaques.

Identical tau filaments in subacute sclerosing panencephalitis and chronic traumatic encephalopathy

This study shows that tau filaments in subacute sclerosing panencephalitis and chronic traumatic encephalopathy have identical structural features.

Tau Filaments from Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) adopt the CTE Fold

This study uses cryo-EM to show that tau filaments in ALS/PDC share the CTE fold, suggesting environmental causes for the disease.

Cryo-EM structures of amyloid-beta filaments with the Arctic mutation (E22G) from human and mouse brains

The paper reports cryo-EM structures of amyloid-beta filaments with the Arctic mutation from human and mouse brains, revealing structural differences and conformational changes.

New SNCA mutation and structures of α-synuclein filaments from juvenile-onset synucleinopathy

The paper identifies a SNCA mutation causing juvenile-onset synucleinopathy and describes the structural features of α-synuclein filaments associated with the disease.

Cryo-EM structures of α-synuclein filaments from Parkinson's disease and dementia with Lewy bodies

The paper reports cryo-EM structures of α-synuclein filaments from Parkinson's disease, PD dementia, and dementia with Lewy bodies, showing they are composed of a single protofilament distinct from those in multiple system atrophy.

Age-dependent formation of TMEM106B amyloid filaments in human brain

This study identifies age-dependent formation of TMEM106B amyloid filaments in human brains using cryo-EM, showing they appear in older individuals but not younger ones.

Assembly of recombinant tau into filaments identical to those of Alzheimer's disease and chronic traumatic encephalopathy

This study reports in vitro assembly of recombinant tau into filaments structurally similar to those in Alzheimer's disease and chronic traumatic encephalopathy using cryo-EM.