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Article
Open AccessCleaved TMEM106B forms amyloid aggregates in central and peripheral nervous systems
Filaments made of residues 120-254 of transmembrane protein 106B (TMEM106B) form in an age-dependent manner and can be extracted from the brains of neurologically normal individuals and those of subjects with ...
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Article
Open AccessData-driven regularization lowers the size barrier of cryo-EM structure determination
Macromolecular structure determination by electron cryo-microscopy (cryo-EM) is limited by the alignment of noisy images of individual particles. Because smaller particles have weaker signals, alignment errors...
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Article
Open AccessDisease-specific tau filaments assemble via polymorphic intermediates
Intermediate species in the assembly of amyloid filaments are believed to play a central role in neurodegenerative diseases and may constitute important targets for therapeutic intervention1,2. However, structura...
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Article
Open AccessNew SNCA mutation and structures of α-synuclein filaments from juvenile-onset synucleinopathy
A 21-nucleotide duplication in one allele of SNCA was identified in a previously described disease with abundant α-synuclein inclusions that we now call juvenile-onset synucleinopathy (JOS). This mutation transla...
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Article
Open AccessCryo-EM structures of amyloid-β filaments with the Arctic mutation (E22G) from human and mouse brains
The Arctic mutation, encoding E693G in the amyloid precursor protein (APP) gene [E22G in amyloid-β (Aβ)], causes dominantly inherited Alzheimer’s disease. Here, we report the high-resolution cryo-EM structures of...
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Article
Open AccessAge-dependent formation of TMEM106B amyloid filaments in human brains
Many age-dependent neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, are characterized by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-β, α-synuc...
