Cryo-EM structures of amyloid-β and tau filaments in Down syndrome.

Autor: Fernandez A; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA., Hoq MR; Department of Biological Sciences, Markey Center for Structural Biology, Purdue University, West Lafayette, IN, USA., Hallinan GI; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA., Li D; Department of Biological Sciences, Markey Center for Structural Biology, Purdue University, West Lafayette, IN, USA., Bharath SR; Department of Biological Sciences, Markey Center for Structural Biology, Purdue University, West Lafayette, IN, USA., Vago FS; Department of Biological Sciences, Markey Center for Structural Biology, Purdue University, West Lafayette, IN, USA., Zhang X; Department of Biological Sciences, Markey Center for Structural Biology, Purdue University, West Lafayette, IN, USA., Ozcan KA; Department of Biological Sciences, Markey Center for Structural Biology, Purdue University, West Lafayette, IN, USA., Newell KL; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA., Garringer HJ; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA., Jiang W; Department of Biological Sciences, Markey Center for Structural Biology, Purdue University, West Lafayette, IN, USA. jiang12@purdue.edu., Ghetti B; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. bghetti@iupui.edu., Vidal R; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. rvidal@iupui.edu.; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA. rvidal@iupui.edu.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2024 Jun; Vol. 31 (6), pp. 903-909. Date of Electronic Publication: 2024 Mar 29.
DOI: 10.1038/s41594-024-01252-3
Abstrakt: Adult individuals with Down syndrome (DS) develop Alzheimer disease (AD). Whether there is a difference between AD in DS and AD regarding the structure of amyloid-β (Aβ) and tau filaments is unknown. Here we report the structure of Aβ and tau filaments from two DS brains. We found two Aβ 40 filaments (types IIIa and IIIb) that differ from those previously reported in sporadic AD and two types of Aβ 42 filaments (I and II) identical to those found in sporadic and familial AD. Tau filaments (paired helical filaments and straight filaments) were identical to those in AD, supporting the notion of a common mechanism through which amyloids trigger aggregation of tau. This knowledge is important for understanding AD in DS and assessing whether adults with DS could be included in AD clinical trials.
(© 2024. The Author(s).)
Databáze: MEDLINE
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