Cryo-electron microscopy of brain tissue from two individuals with Down syndrome showed amyloid-β (Aβ) and tau filaments identical to those found in individuals with sporadic or dominantly inherited Alzheimer disease (AD), but also two types of Aβ40 filaments with distinct structures different from those previously reported in AD and cerebral amyloid angiopathy.
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References
Fortea, J. et al. Alzheimer’s disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol. 20, 930–942 (2021). A review article on the natural history and clinical presentation of DS.
Lott, I. T. & Head, E. Dementia in Down syndrome: unique insights for Alzheimer disease research. Nat. Rev. Neurol. 15, 135–147 (2019). A detailed review article of the clinical and neuropathological similarities between AD and DS.
Yang, Y. et al. Cryo-EM structures of amyloid-β 42 filaments from human brains. Science. 375, 167–172 (2022). The authors of this paper report, to our knowledge, the first characterization of Aβ42 filaments from human brains.
Yang, Y. et al. Cryo-EM structures of Aβ40 filaments from the leptomeninges of individuals with Alzheimer’s disease and cerebral amyloid angiopathy. Acta Neuropathol. Commun. 11, 191 (2023). This paper characterizes vascular amyloid deposits in AD and cerebral amyloid angiopathy.
Shi, Y. et al. Structure-based classification of tauopathies. Nature 598, 359–363 (2021). This paper reports a detailed study of the structure of tau aggregates across the spectrum of tauopathies.
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This is a summary of: Fernandez, A. et al. Cryo-EM structures of amyloid-β and tau filaments in Down syndrome. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-024-01252-3 (2024).
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High-resolution structures of amyloid-β and tau aggregates in individuals with Down syndrome. Nat Struct Mol Biol (2024). https://doi.org/10.1038/s41594-024-01254-1
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DOI: https://doi.org/10.1038/s41594-024-01254-1
