Amyloid β-Protein Assembly and Alzheimer's Disease: Dodecamers of Aβ42, but Not of Aβ40, Seed Fibril Formation

Journal of the American Chemical Society
Nicholas J EconomouMichael T Bowers

Abstract

Evidence suggests that oligomers of the 42-residue form of the amyloid β-protein (Aβ), Aβ42, play a critical role in the etiology of Alzheimer's disease (AD). Here we use high resolution atomic force microscopy to directly image populations of small oligomers of Aβ42 that occur at the earliest stages of aggregation. We observe features that can be attributed to a monomer and to relatively small oligomers, including dimers, hexamers, and dodecamers. We discovered that Aβ42 hexamers and dodecamers quickly become the dominant oligomers after peptide solubilization, even at low (1 μM) concentrations and short (5 min) incubation times. Soon after (≥10 min), dodecamers are observed to seed the formation of extended, linear preprotofibrillar β-sheet structures. The preprotofibrils are a single Aβ42 layer in height and can extend several hundred nanometers in length. To our knowledge this is the first report of structures of this type. In each instance the preprotofibril is associated off center with a single layer of a dodecamer. Protofibril formation continues at longer times, but is accompanied by the formation of large, globular aggregates. Aβ40, by contrast, does not significantly form the hexamer or dodecamer but instead produces...Continue Reading

References

Apr 10, 1992·Science·J A Hardy, G A Higgins
Oct 1, 1995·European Journal of Biochemistry·H StichtP Rösch
Mar 1, 1995·Annals of Neurology·S G Younkin
Feb 1, 1996·Journal of Protein Chemistry·W B StineG A Krafft
Feb 1, 1997·Chemistry & Biology·J D HarperP T Lansbury
Aug 29, 1997·The Journal of Biological Chemistry·D M WalshD B Teplow
Dec 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Gal BitanDavid B Teplow
Feb 17, 2005·Journal of the American Chemical Society·Summer L BernsteinMichael T Bowers
Feb 22, 2005·The Journal of Biological Chemistry·Angelo DemuroCharles G Glabe
Feb 28, 2006·Journal of Molecular Biology·Iris A MastrangeloSteven O Smith
Feb 28, 2006·Protein Science : a Publication of the Protein Society·Andrij BaumketnerJoan-Emma Shea
Mar 17, 2006·Nature·Sylvain LesnéKaren H Ashe
Sep 18, 2007·Journal of Molecular Biology·E Prabhu RamanDmitri K Klimov
Oct 11, 2008·The Journal of Biological Chemistry·Robin RoychaudhuriDavid B Teplow
Apr 24, 2009·Journal of the American Chemical Society·Megan M MurrayMichael T Bowers
Apr 13, 2010·Nature Structural & Molecular Biology·Mahiuddin AhmedSteven O Smith
Jul 6, 2011·Biochemical and Biophysical Research Communications·Subramanian VivekanandanAyyalusamy Ramamoorthy
Nov 17, 2012·Journal of Molecular Biology·Robin RoychaudhuriDavid B Teplow
Apr 25, 2013·Nanoscale·Xingfei ZhouYi Zhang
May 1, 2013·Journal of the American Chemical Society·Wei QiangRobert Tycko
May 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Samuel I A CohenTuomas P J Knowles
Aug 29, 2013·Alzheimer's Research & Therapy·David B Teplow
Dec 4, 2013·The Journal of Physical Chemistry. B·Nathan A BernhardtUlrich H E Hansmann
Dec 11, 2013·Biosensors & Bioelectronics·Francis T HaneZoya Leonenko
Jun 13, 2015·Biochemistry·Ziao FuSteven O Smith

❮ Previous
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Citations

Aug 29, 2016·Journal of Alzheimer's Disease : JAD·Olga M SelivanovaOxana V Galzitskaya
Oct 28, 2016·The Journal of Physical Chemistry. B·Li WangMichael T Bowers
Nov 1, 2016·Journal of the American Chemical Society·Richard HaburcakBing Xu
Jun 18, 2017·Neurotoxicity Research·Zhong-Yue LvLan Tan
Nov 16, 2016·Molecular BioSystems·L Dorosh, M Stepanova
May 17, 2018·Chemical Communications : Chem Comm·Giovanni BellomoClaudio Luchinat
May 31, 2018·Journal of Alzheimer's Disease : JAD·Erika N ClineWilliam L Klein
Jan 20, 2018·Protein Science : a Publication of the Protein Society·Thanh D DoMichael T Bowers
Jul 27, 2018·Metallomics : Integrated Biometal Science·Hyuck Jin LeeMi Hee Lim
Sep 29, 2018·Journal of Molecular Recognition : JMR·Daniel J MermelsteinRoss C Walker
Mar 17, 2018·Biochemistry. Biokhimii︠a︡·O V GalzitskayaO M Selivanova
Nov 23, 2019·Current Topics in Medicinal Chemistry·Maria J E Visser, Etheresia Pretorius
Nov 30, 2016·Faraday Discussions·Wei-Tao DouHe Tian
Jun 1, 2017·Scientific Reports·Martin WolffLuitgard Nagel-Steger
Jul 4, 2017·Journal of Alzheimer's Disease : JAD·Oxana V Galzitskaya, Olga M Selivanova
Apr 5, 2017·Annual Review of Analytical Chemistry·Christian Bleiholder, Michael T Bowers
Feb 24, 2019·The Journal of Chemical Physics·Wenhui XiVijayaraghavan Rangachari
Aug 12, 2017·The Journal of Chemical Physics·Mark N JoswiakBaron Peters
Mar 28, 2019·Scientific Reports·Marta Querol-VilasecaAlberto Lleó
Oct 14, 2019·Journal of Pharmaceutical and Biomedical Analysis·Angela De SimoneVincenza Andrisano
Feb 24, 2021·Journal of the American Chemical Society·Veronica LaosMichael T Bowers
Mar 7, 2021·Chemistry and Physics of Lipids·Sara García-ViñualesDanilo Milardi
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anatoly S UrbanEduard V Bocharov
Nov 9, 2016·Journal of the American Society for Mass Spectrometry·Xueqin PangLingjun Li
May 2, 2018·Journal of the American Society for Mass Spectrometry·Matthew A DowneyMichael T Bowers
Jun 23, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yuying HuangQiang Fu

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