@article{shiCryoEMStructuresTau2021,
	title = {Cryo-{EM} structures of tau filaments from Alzheimer’s disease with {PET} ligand {APN}-1607},
	volume = {141},
	issn = {0001-6322, 1432-0533},
	url = {https://link.springer.com/10.1007/s00401-021-02294-3},
	doi = {10.1007/s00401-021-02294-3},
	abstract = {Abstract
            Tau and Aβ assemblies of Alzheimer’s disease ({AD}) can be visualized in living subjects using positron emission tomography ({PET}). Tau assemblies comprise paired helical and straight filaments ({PHFs} and {SFs}). {APN}-1607 ({PM}-{PBB}3) is a recently described {PET} ligand for {AD} and other tau proteinopathies. Since it is not known where in the tau folds {PET} ligands bind, we used electron cryo-microscopy (cryo-{EM}) to determine the binding sites of {APN}-1607 in the Alzheimer fold. We identified two major sites in the β-helix of {PHFs} and {SFs} and a third major site in the C-shaped cavity of {SFs}. In addition, we report that tau filaments from posterior cortical atrophy ({PCA}) and primary age-related tauopathy ({PART}) are identical to those from {AD}. In support, fluorescence labelling showed binding of {APN}-1607 to intraneuronal inclusions in {AD}, {PART} and {PCA}. Knowledge of the binding modes of {APN}-1607 to tau filaments may lead to the development of new ligands with increased specificity and binding activity. We show that cryo-{EM} can be used to identify the binding sites of small molecules in amyloid filaments.},
	pages = {697--708},
	number = {5},
	journaltitle = {Acta Neuropathologica},
	shortjournal = {Acta Neuropathol},
	author = {Shi, Yang and Murzin, Alexey G. and Falcon, Benjamin and Epstein, Alexander and Machin, Jonathan and Tempest, Paul and Newell, Kathy L. and Vidal, Ruben and Garringer, Holly J. and Sahara, Naruhiko and Higuchi, Makoto and Ghetti, Bernardino and Jang, Ming-Kuei and Scheres, Sjors H. W. and Goedert, Michel},
	urldate = {2022-03-09},
	date = {2021-05},
	langid = {english},
	keywords = {peer-reviewed},
}