Antibodies Raised Against an Aβ Oligomer Mimic Recognize Pathological Features in Alzheimer’s Disease and Associated Amyloid-Disease Brain Tissue

Kreutzer, Adam G.; Parrocha, Chelsea Marie T.; Haerianardakani, Sepehr; Guaglianone, Gretchen; Nguyen, Jennifer T.; Diab, Michelle N.; Yong, William; Perez-Rosendahl, Mari; Head, Elizabeth; Nowick, James S.

doi:10.1021/acscentsci.3c00592

Antibodies Raised Against an Aβ Oligomer Mimic Recognize Pathological Features in Alzheimer’s Disease and Associated Amyloid-Disease Brain Tissue

Journal Article · Thu Dec 21 00:00:00 EST 2023 · ACS Central Science

DOI:https://doi.org/10.1021/acscentsci.3c00592· OSTI ID:2471057

^[1]; ^[1]; ^[1]; ^[1]; Nguyen, Jennifer T. ^[1]; Diab, Michelle N. ^[1]; Yong, William ^[1]; Perez-Rosendahl, Mari ^[1]; Head, Elizabeth ^[1]; ^[1]

University of California, Irvine, CA (United States)

Antibodies that target the β-amyloid peptide (Aβ) and its associated assemblies are important tools in Alzheimer’s disease research and have emerged as promising Alzheimer’s disease therapies. This paper reports the creation and characterization of a triangular Aβ trimer mimic composed of Aβ_17–36 β-hairpins and the generation and study of polyclonal antibodies raised against the Aβ trimer mimic. The Aβ trimer mimic is covalently stabilized by three disulfide bonds at the corners of the triangular trimer to create a homogeneous oligomer. Structural, biophysical, and cell-based studies demonstrate that the Aβ trimer mimic shares characteristics with oligomers of full-length Aβ. X-ray crystallography elucidates the structure of the trimer and reveals that four copies of the trimer assemble to form a dodecamer. SDS-PAGE, size exclusion chromatography, and dynamic light scattering reveal that the trimer also forms higher-order assemblies in solution. Cell-based toxicity assays show that the trimer elicits LDH release, decreases ATP levels, and activates caspase-3/7 mediated apoptosis. Immunostaining studies on brain slices from people who lived with Alzheimer’s disease and people who lived with Down syndrome reveal that the polyclonal antibodies raised against the Aβ trimer mimic recognize pathological features including different types of Aβ plaques and cerebral amyloid angiopathy.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)

Sponsoring Organization:: Cancer Center Support Grant; Center for Complex Biological Systems Support Grant; National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2471057

Journal Information:: ACS Central Science, Journal Name: ACS Central Science Journal Issue: 1 Vol. 10; ISSN 2374-7943

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

References (128)

A Prospective Study of Alzheimer Disease in Down Syndrome Lai, F.; Williams, R. S. Archives of Neurology, Vol. 46, Issue 8 https://doi.org/10.1001/archneur.1989.00520440031017	journal	August 1989
Donanemab in Early Symptomatic Alzheimer Disease Sims, John R.; Zimmer, Jennifer A.; Evans, Cynthia D. JAMA, Vol. 330, Issue 6 https://doi.org/10.1001/jama.2023.13239	journal	August 2023
Correlation of Specific Amyloid-β Oligomers With Tau in Cerebrospinal Fluid From Cognitively Normal Older Adults Handoko, Maureen; Grant, Marianne; Kuskowski, Michael JAMA Neurology, Vol. 70, Issue 5 https://doi.org/10.1001/jamaneurol.2013.48	journal	May 2013
The biogenesis and biology of amyloid β oligomers in the brain Ashe, Karen Hsiao Alzheimer's & Dementia, Vol. 16, Issue 11 https://doi.org/10.1002/alz.12084	journal	June 2020
Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019 Knopman, David S.; Jones, David T.; Greicius, Michael D. Alzheimer's & Dementia, Vol. 17, Issue 4 https://doi.org/10.1002/alz.12213	journal	November 2020
A Hexameric Peptide Barrel as Building Block of Amyloid-β Protofibrils Lendel, Christofer; Bjerring, Morten; Dubnovitsky, Anatoly Angewandte Chemie International Edition, Vol. 53, Issue 47 https://doi.org/10.1002/anie.201406357	journal	September 2014
A Palette of Fluorescent Thiophene‐Based Ligands for the Identification of Protein Aggregates Shirani, Hamid; Linares, Mathieu; Sigurdson, Christina J. Chemistry – A European Journal, Vol. 21, Issue 43 https://doi.org/10.1002/chem.201502999	journal	September 2015
Dementia in people with Down's syndrome Tyrrell, Janette; Cosgrave, Mary; McCarron, Mary International Journal of Geriatric Psychiatry, Vol. 16, Issue 12 https://doi.org/10.1002/gps.502	journal	December 2001
Neuropathology of Alzheimer's Disease Perl, Daniel P. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine, Vol. 77, Issue 1 https://doi.org/10.1002/msj.20157	journal	January 2010
Peptide Compositions of the Cerebrovascular and Senile Plaque Core Amyloid Deposits of Alzheimer′s Disease Miller, D. L.; Papayannopoulos, I. A.; Styles, J. Archives of Biochemistry and Biophysics, Vol. 301, Issue 1 https://doi.org/10.1006/abbi.1993.1112	journal	February 1993
Diffuse type of senile plaques in the brains of Alzheimer-type dementia Yamaguchi, H.; Hirai, S.; Morimatsu, M. Acta Neuropathologica, Vol. 77, Issue 2 https://doi.org/10.1007/BF00687420	journal	March 1988
Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease Wisniewski, H. M.; Bancher, C.; Barcikowska, M. Acta Neuropathologica, Vol. 78, Issue 4 https://doi.org/10.1007/BF00688170	journal	January 1989
Diffusible, highly bioactive oligomers represent a critical minority of soluble Aβ in Alzheimer’s disease brain Hong, Wei; Wang, Zemin; Liu, Wen Acta Neuropathologica, Vol. 136, Issue 1 https://doi.org/10.1007/s00401-018-1846-7	journal	April 2018
The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer’s disease Boon, Baayla D. C.; Bulk, Marjolein; Jonker, Allert J. Acta Neuropathologica, Vol. 140, Issue 6 https://doi.org/10.1007/s00401-020-02198-8	journal	September 2020
The pattern of acquisition of plaques and tangles in the brains of patients under 50 years of age with Down's syndrome Mann, David M. A.; Esiri, Margaret M. Journal of the Neurological Sciences, Vol. 89, Issue 2-3 https://doi.org/10.1016/0022-510X(89)90019-1	journal	February 1989
Cerebral amyloid angiopathy and alzheimer's disease: two entities or one? Vinters, Harry V. Journal of the Neurological Sciences, Vol. 112, Issue 1-2 https://doi.org/10.1016/0022-510X(92)90124-4	journal	October 1992
The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease Price, J. L.; Davis, P. B.; Morris, J. C. Neurobiology of Aging, Vol. 12, Issue 4 https://doi.org/10.1016/0197-4580(91)90006-6	journal	July 1991
βA4 deposits are constant in the brain of the oldest old: An immunocytochemical study of 20 french centenarians Delaère, Pia; He, Yi; Fayet, Guillemette Neurobiology of Aging, Vol. 14, Issue 2 https://doi.org/10.1016/0197-4580(93)90096-T	journal	March 1993
Preamyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals Tagliavini, Fabrizio; Giaccone, Giorgio; Frangione, Blas Neuroscience Letters, Vol. 93, Issue 2-3 https://doi.org/10.1016/0304-3940(88)90080-8	journal	November 1988
Appearance of Sodium Dodecyl Sulfate-Stable Amyloid β-Protein (Aβ) Dimer in the Cortex During Aging Enya, Miho; Morishima-Kawashima, Maho; Yoshimura, Masahiro The American Journal of Pathology, Vol. 154, Issue 1 https://doi.org/10.1016/S0002-9440(10)65273-X	journal	January 1999
Monoclonal antibodies as structural probes of surface residues in the regulatory subunit of cAMP-dependent protein kinase II from porcine heart. Weldon, S. L.; Mumby, M. C.; Beavo, J. A. Journal of Biological Chemistry, Vol. 258, Issue 2 https://doi.org/10.1016/S0021-9258(18)33168-5	journal	January 1983
Early senile plaques in Alzheimer's disease demonstrated by histochemistry, immunocytochemistry, and electron microscopy Ikeda, Shu-Ichi; Yanagisawa, Nobuo; Allsop, David Human Pathology, Vol. 21, Issue 12 https://doi.org/10.1016/S0046-8177(06)80034-1	journal	December 1990
Intracellular accumulation of β-amyloid1–42 in neurons is facilitated by the α7 nicotinic acetylcholine receptor in Alzheimer’s disease Nagele, R. G.; D’Andrea, M. R.; Anderson, W. J. Neuroscience, Vol. 110, Issue 2 https://doi.org/10.1016/S0306-4522(01)00460-2	journal	March 2002
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade Jack, Clifford R.; Knopman, David S.; Jagust, William J. The Lancet Neurology, Vol. 9, Issue 1 https://doi.org/10.1016/S1474-4422(09)70299-6	journal	January 2010
Solid-state NMR analysis of the β-strand orientation of the protofibrils of amyloid β-protein Doi, Takashi; Masuda, Yuichi; Irie, Kazuhiro Biochemical and Biophysical Research Communications, Vol. 428, Issue 4 https://doi.org/10.1016/j.bbrc.2012.10.096	journal	November 2012
Exploring amyloid oligomers with peptide model systems Samdin, Tuan D.; Kreutzer, Adam G.; Nowick, James S. Current Opinion in Chemical Biology, Vol. 64 https://doi.org/10.1016/j.cbpa.2021.05.004	journal	October 2021
Molecular Structure of β-Amyloid Fibrils in Alzheimer’s Disease Brain Tissue Lu, Jun-Xia; Qiang, Wei; Yau, Wai-Ming Cell, Vol. 154, Issue 6 https://doi.org/10.1016/j.cell.2013.08.035	journal	September 2013
Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration Liu, Peng; Reed, Miranda N.; Kotilinek, Linda A. Cell Reports, Vol. 11, Issue 11 https://doi.org/10.1016/j.celrep.2015.05.021	journal	June 2015
High-definition characterization of cerebral β-amyloid angiopathy in Alzheimer's disease Soontornniyomkij, Virawudh; Choi, Cecilia; Pomakian, Justine Human Pathology, Vol. 41, Issue 11 https://doi.org/10.1016/j.humpath.2010.04.011	journal	November 2010
Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Sperling, Reisa A.; Aisen, Paul S.; Beckett, Laurel A. Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.003	journal	May 2011
Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis Ovod, Vitaliy; Ramsey, Kara N.; Mawuenyega, Kwasi G. Alzheimer's & Dementia, Vol. 13, Issue 8 https://doi.org/10.1016/j.jalz.2017.06.2266	journal	July 2017
Human cerebral vascular amyloid contains both antiparallel and parallel in-register Aβ40 fibrils Irizarry, Brandon A.; Davis, Judianne; Zhu, Xiaoyue Journal of Biological Chemistry, Vol. 297, Issue 5 https://doi.org/10.1016/j.jbc.2021.101259	journal	November 2021
Oligomeric Intermediates in Amyloid Formation: Structure Determination and Mechanisms of Toxicity Fändrich, Marcus Journal of Molecular Biology, Vol. 421, Issue 4-5 https://doi.org/10.1016/j.jmb.2012.01.006	journal	August 2012
The Alzheimer's Amyloid-β(1–42) Peptide Forms Off-Pathway Oligomers and Fibrils That Are Distinguished Structurally by Intermolecular Organization Tay, William M.; Huang, Danting; Rosenberry, Terrone L. Journal of Molecular Biology, Vol. 425, Issue 14 https://doi.org/10.1016/j.jmb.2013.04.003	journal	July 2013
An amyloid-β protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer's disease Lord, Anna; Gumucio, Astrid; Englund, Hillevi Neurobiology of Disease, Vol. 36, Issue 3 https://doi.org/10.1016/j.nbd.2009.08.007	journal	December 2009
A Plaque-Specific Antibody Clears Existing β-amyloid Plaques in Alzheimer's Disease Mice DeMattos, Ronald B.; Lu, Jirong; Tang, Ying Neuron, Vol. 76, Issue 5 https://doi.org/10.1016/j.neuron.2012.10.029	journal	December 2012
Elucidating the Structures of Amyloid Oligomers with Macrocyclic β-Hairpin Peptides: Insights into Alzheimer’s Disease and Other Amyloid Diseases Kreutzer, Adam G.; Nowick, James S. Accounts of Chemical Research, Vol. 51, Issue 3 https://doi.org/10.1021/acs.accounts.7b00554	journal	March 2018
Nascent Hairpins in Proteins: Identifying Turn Loci and Quantitating Turn Contributions to Hairpin Stability Anderson, Jordan M.; Jurban, Brice; Huggins, Kelly N. L. Biochemistry, Vol. 55, Issue 39 https://doi.org/10.1021/acs.biochem.6b00732	journal	September 2016
Experimental Constraints on Quaternary Structure in Alzheimer's β-Amyloid Fibrils ^† Petkova, Aneta T.; Yau, Wai-Ming; Tycko, Robert Biochemistry, Vol. 45, Issue 2 https://doi.org/10.1021/bi051952q	journal	January 2006
Structural Characterization of a Soluble Amyloid β-Peptide Oligomer Yu, Liping; Edalji, Rohinton; Harlan, John E. Biochemistry, Vol. 48, Issue 9 https://doi.org/10.1021/bi802046n	journal	March 2009
Monoclonal Antibody Against the Turn of the 42-Residue Amyloid β-Protein at Positions 22 and 23 Murakami, Kazuma; Horikoshi-Sakuraba, Yuko; Murata, Nakaba ACS Chemical Neuroscience, Vol. 1, Issue 11 https://doi.org/10.1021/cn100072e	journal	September 2010
Minimization and Optimization of Designed β-Hairpin Folds Andersen, Niels H.; Olsen, Katherine A.; Fesinmeyer, R. Matthew Journal of the American Chemical Society, Vol. 128, Issue 18 https://doi.org/10.1021/ja054971w	journal	April 2006
X-ray Crystallographic Structures of Trimers and Higher-Order Oligomeric Assemblies of a Peptide Derived from Aβ _17–36 Spencer, Ryan K.; Li, Hao; Nowick, James S. Journal of the American Chemical Society, Vol. 136, Issue 15 https://doi.org/10.1021/ja5017409	journal	April 2014
Phenylalanine Mutation to Cyclohexylalanine Facilitates Triangular Trimer Formation by β-Hairpins Derived from Aβ Haerianardakani, Sepehr; Kreutzer, Adam G.; Salveson, Patrick J. Journal of the American Chemical Society, Vol. 142, Issue 49 https://doi.org/10.1021/jacs.0c09281	journal	November 2020
X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ_17–36 β-Hairpin Kreutzer, Adam G.; Hamza, Imane L.; Spencer, Ryan K. Journal of the American Chemical Society, Vol. 138, Issue 13 https://doi.org/10.1021/jacs.6b01332	journal	March 2016
Atomic Resolution Structure of Monomorphic Aβ ₄₂ Amyloid Fibrils Colvin, Michael T.; Silvers, Robert; Ni, Qing Zhe Journal of the American Chemical Society, Vol. 138, Issue 30 https://doi.org/10.1021/jacs.6b05129	journal	July 2016
Stabilization, Assembly, and Toxicity of Trimers Derived from Aβ Kreutzer, Adam G.; Yoo, Stan; Spencer, Ryan K. Journal of the American Chemical Society, Vol. 139, Issue 2 https://doi.org/10.1021/jacs.6b11748	journal	January 2017
Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo Walsh, Dominic M.; Klyubin, Igor; Fadeeva, Julia V. Nature, Vol. 416, Issue 6880 https://doi.org/10.1038/416535a	journal	April 2002
Post-hoc analysis could give new life to the Alzheimer’s drug aducanumab Arnold, Carrie Nature Medicine https://doi.org/10.1038/d41591-020-00031-z	journal	November 2020
A specific amyloid-β protein assembly in the brain impairs memory Lesné, Sylvain; Koh, Ming Teng; Kotilinek, Linda Nature, Vol. 440, Issue 7082 https://doi.org/10.1038/nature04533	journal	March 2006
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease Sevigny, Jeff; Chiao, Ping; Bussière, Thierry Nature, Vol. 537, Issue 7618 https://doi.org/10.1038/nature19323	journal	August 2016
Structural variation in amyloid-β fibrils from Alzheimer's disease clinical subtypes Qiang, Wei; Yau, Wai-Ming; Lu, Jun-Xia Nature, Vol. 541, Issue 7636 https://doi.org/10.1038/nature20814	journal	January 2017
Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory Shankar, Ganesh M.; Li, Shaomin; Mehta, Tapan H. Nature Medicine, Vol. 14, Issue 8 https://doi.org/10.1038/nm1782	journal	June 2008
The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes Benilova, Iryna; Karran, Eric; De Strooper, Bart Nature Neuroscience, Vol. 15, Issue 3 https://doi.org/10.1038/nn.3028	journal	January 2012
Alzheimer's disease Masters, Colin L.; Bateman, Randall; Blennow, Kaj Nature Reviews Disease Primers, Vol. 1, Issue 1 https://doi.org/10.1038/nrdp.2015.56	journal	October 2015
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide Haass, Christian; Selkoe, Dennis J. Nature Reviews Molecular Cell Biology, Vol. 8, Issue 2 https://doi.org/10.1038/nrm2101	journal	February 2007
De novo design and structural analysis of a model β-hairpin peptide system Ramírez-Alvarado, Marina; Blanco, Francisco J.; Serrano, Luis Nature Structural Biology, Vol. 3, Issue 7 https://doi.org/10.1038/nsb0796-604	journal	July 1996
Aβ(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer's disease Xiao, Yiling; Ma, Buyong; McElheny, Dan Nature Structural & Molecular Biology, Vol. 22, Issue 6 https://doi.org/10.1038/nsmb.2991	journal	May 2015
An in vitro paradigm to assess potential anti-Aβ antibodies for Alzheimer’s disease Jin, Ming; O’Nuallain, Brian; Hong, Wei Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-05068-w	journal	July 2018
Aβ(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage Ciudad, Sonia; Puig, Eduard; Botzanowski, Thomas Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-16566-1	journal	June 2020
Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β Arndt, Joseph W.; Qian, Fang; Smith, Benjamin A. Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-24501-0	journal	April 2018
Monoclonal antibody with conformational specificity for a toxic conformer of amyloid β42 and its application toward the Alzheimer’s disease diagnosis Murakami, Kazuma; Tokuda, Maki; Suzuki, Takashi Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep29038	journal	July 2016
Aβ dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies O’Malley, Tiernan T.; Oktaviani, Nur Alia; Zhang, Dainan Biochemical Journal, Vol. 461, Issue 3 https://doi.org/10.1042/BJ20140219	journal	July 2014
Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease Bateman, Randall J.; Xiong, Chengjie; Benzinger, Tammie L. S. New England Journal of Medicine, Vol. 367, Issue 9 https://doi.org/10.1056/NEJMoa1202753	journal	August 2012
Alzheimer's Disease Querfurth, Henry W.; LaFerla, Frank M. New England Journal of Medicine, Vol. 362, Issue 4 https://doi.org/10.1056/NEJMra0909142	journal	January 2010
Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease Georganopoulou, Dimitra G.; Chang, Lei; Nam, Jwa-Min Proceedings of the National Academy of Sciences, Vol. 102, Issue 7 https://doi.org/10.1073/pnas.0409336102	journal	February 2005
Stabilization of a β-hairpin in monomeric Alzheimer's amyloid-β peptide inhibits amyloid formation Hoyer, Wolfgang; Grönwall, Caroline; Jonsson, Andreas Proceedings of the National Academy of Sciences, Vol. 105, Issue 13 https://doi.org/10.1073/pnas.0711731105	journal	March 2008
Molecular structural basis for polymorphism in Alzheimer's -amyloid fibrils Paravastu, A. K.; Leapman, R. D.; Yau, W. -M. Proceedings of the National Academy of Sciences, Vol. 105, Issue 47 https://doi.org/10.1073/pnas.0806270105	journal	November 2008
Oligomeric amyloid β associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques Koffie, Robert M.; Meyer-Luehmann, Melanie; Hashimoto, Tadafumi Proceedings of the National Academy of Sciences, Vol. 106, Issue 10 https://doi.org/10.1073/pnas.0811698106	journal	March 2009
Stabilization of neurotoxic Alzheimer amyloid- oligomers by protein engineering Sandberg, A.; Luheshi, L. M.; Sollvander, S. Proceedings of the National Academy of Sciences, Vol. 107, Issue 35 https://doi.org/10.1073/pnas.1001740107	journal	August 2010
Soluble amyloid -protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration Jin, M.; Shepardson, N.; Yang, T. Proceedings of the National Academy of Sciences, Vol. 108, Issue 14 https://doi.org/10.1073/pnas.1017033108	journal	March 2011
Antiparallel -sheet architecture in Iowa-mutant -amyloid fibrils Qiang, W.; Yau, W. -M.; Luo, Y. Proceedings of the National Academy of Sciences, Vol. 109, Issue 12 https://doi.org/10.1073/pnas.1111305109	journal	March 2012
Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril Wälti, Marielle Aulikki; Ravotti, Francesco; Arai, Hiromi Proceedings of the National Academy of Sciences, Vol. 113, Issue 34 https://doi.org/10.1073/pnas.1600749113	journal	July 2016
Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments Serra-Batiste, Montserrat; Ninot-Pedrosa, Martí; Bayoumi, Mariam Proceedings of the National Academy of Sciences, Vol. 113, Issue 39 https://doi.org/10.1073/pnas.1605104113	journal	September 2016
Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue Ghosh, Ujjayini; Thurber, Kent R.; Yau, Wai-Ming Proceedings of the National Academy of Sciences, Vol. 118, Issue 4 https://doi.org/10.1073/pnas.2023089118	journal	January 2021
Probing differences among Aβ oligomers with two triangular trimers derived from Aβ Kreutzer, Adam G.; Guaglianone, Gretchen; Yoo, Stan Proceedings of the National Academy of Sciences, Vol. 120, Issue 22 https://doi.org/10.1073/pnas.2219216120	journal	May 2023
Diffusible, nonfibrillar ligands derived from A 1-42 are potent central nervous system neurotoxins Lambert, M. P.; Barlow, A. K.; Chromy, B. A. Proceedings of the National Academy of Sciences, Vol. 95, Issue 11 https://doi.org/10.1073/pnas.95.11.6448	journal	May 1998
Isolation and Characterization of Patient-derived, Toxic, High Mass Amyloid β-Protein (Aβ) Assembly from Alzheimer Disease Brains Noguchi, Akihiko; Matsumura, Satoko; Dezawa, Mari Journal of Biological Chemistry, Vol. 284, Issue 47 https://doi.org/10.1074/jbc.M109.000208	journal	November 2009
Two Distinct Amyloid β-Protein (Aβ) Assembly Pathways Leading to Oligomers and Fibrils Identified by Combined Fluorescence Correlation Spectroscopy, Morphology, and Toxicity Analyses Matsumura, Satoko; Shinoda, Keiko; Yamada, Mayumi Journal of Biological Chemistry, Vol. 286, Issue 13 https://doi.org/10.1074/jbc.M110.181313	journal	April 2011
Amyloid-β Annular Protofibrils Evade Fibrillar Fate in Alzheimer Disease Brain Lasagna-Reeves, Cristian A.; Glabe, Charles G.; Kayed, Rakez Journal of Biological Chemistry, Vol. 286, Issue 25 https://doi.org/10.1074/jbc.M111.236257	journal	June 2011
Solid-state NMR Reveals a Close Structural Relationship between Amyloid-β Protofibrils and Oligomers Scheidt, Holger A.; Morgado, Isabel; Huster, Daniel Journal of Biological Chemistry, Vol. 287, Issue 27 https://doi.org/10.1074/jbc.M112.367474	journal	June 2012
Monoclonal Antibodies as Structural Probes for Oligomeric Human Interferon-Gamma Le, Junming; Chang, Tse Wen; Liu, Victor Journal of Interferon Research, Vol. 5, Issue 3 https://doi.org/10.1089/jir.1985.5.445	journal	January 1985
Brain amyloid-β oligomers in ageing and Alzheimer’s disease Lesné, Sylvain E.; Sherman, Mathew A.; Grant, Marianne Brain, Vol. 136, Issue 5 https://doi.org/10.1093/brain/awt062	journal	April 2013
Rapidly progressive Alzheimer’s disease features distinct structures of amyloid-β Cohen, Mark L.; Kim, Chae; Haldiman, Tracy Brain, Vol. 138, Issue 4 https://doi.org/10.1093/brain/awv006	journal	February 2015
Identification of neurotoxic cross-linked amyloid-β dimers in the Alzheimer’s brain Brinkmalm, Gunnar; Hong, Wei; Wang, Zemin Brain, Vol. 142, Issue 5 https://doi.org/10.1093/brain/awz066	journal	April 2019
Amyloid beta oligomers induce impairment of neuronal insulin receptors Zhao, Wei‐Qin; De Felice, Fernanda G.; Fernandez, Sara The FASEB Journal, Vol. 22, Issue 1 https://doi.org/10.1096/fj.06-7703com	journal	August 2007
The Pathogenesis of Senile Plaques Dickson, Dennis W. Journal of Neuropathology and Experimental Neurology, Vol. 56, Issue 4 https://doi.org/10.1097/00005072-199704000-00001	journal	April 1997
Both lipopolysaccharide and lipoteichoic acids potently induce anomalous fibrin amyloid formation: assessment with novel Amytracker™ stains Pretorius, Etheresia; Page, Martin J.; Hendricks, Lisa Journal of The Royal Society Interface, Vol. 15, Issue 139 https://doi.org/10.1098/rsif.2017.0941	journal	February 2018
Early Senile Plaques in Down'S Syndrome Brains show a Close Relationship with cell Bodies of Neurons Allsop, D.; Haga, S. I.; Haga, C. Neuropathology and Applied Neurobiology, Vol. 15, Issue 6 https://doi.org/10.1111/j.1365-2990.1989.tb01252.x	journal	December 1989
Monoclonal antibodies that target pathological assemblies of Aβ Lambert, Mary P.; Velasco, Pauline T.; Chang, Lei Journal of Neurochemistry, Vol. 100, Issue 1 https://doi.org/10.1111/j.1471-4159.2006.04157.x	journal	August 2006
Sensitive ELISA detection of amyloid‐β protofibrils in biological samples Englund, Hillevi; Sehlin, Dag; Johansson, Ann‐Sofi Journal of Neurochemistry, Vol. 103, Issue 1 https://doi.org/10.1111/j.1471-4159.2007.04759.x	journal	June 2007
The conformational epitope for a new Aβ42 protofibril-selective antibody partially overlaps with the peptide N-terminal region Colvin, Benjamin A.; Rogers, Victoria A.; Kulas, Joshua A. Journal of Neurochemistry, Vol. 143, Issue 6 https://doi.org/10.1111/jnc.14211	journal	November 2017
Review: Vascular dementia: clinicopathologic and genetic considerations Vinters, H. V.; Zarow, C.; Borys, E. Neuropathology and Applied Neurobiology, Vol. 44, Issue 3 https://doi.org/10.1111/nan.12472	journal	March 2018
Effects of secreted oligomers of amyloid β‐protein on hippocampal synaptic plasticity: a potent role for trimers Townsend, Matthew; Shankar, Ganesh M.; Mehta, Tapan The Journal of Physiology, Vol. 572, Issue 2 https://doi.org/10.1113/jphysiol.2005.103754	journal	April 2006
Alzheimer's Disease Is a Synaptic Failure Selkoe, D. J. Science, Vol. 298, Issue 5594 https://doi.org/10.1126/science.1074069	journal	October 2002
Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis Kayed, R. Science, Vol. 300, Issue 5618 https://doi.org/10.1126/science.1079469	journal	April 2003
Fibril structure of amyloid-β(1–42) by cryo–electron microscopy Gremer, Lothar; Schölzel, Daniel; Schenk, Carla Science, Vol. 358, Issue 6359 https://doi.org/10.1126/science.aao2825	journal	September 2017
Amyloid β oligomers constrict human capillaries in Alzheimer’s disease via signaling to pericytes Nortley, Ross; Korte, Nils; Izquierdo, Pablo Science, Vol. 365, Issue 6450 https://doi.org/10.1126/science.aav9518	journal	July 2019
Treatments for Alzheimer's disease emerge Selkoe, Dennis J. Science, Vol. 373, Issue 6555 https://doi.org/10.1126/science.abi6401	journal	August 2021
Alzheimer’s drugs: Does reducing amyloid work?—Response Selkoe, Dennis J. Science, Vol. 374, Issue 6567 https://doi.org/10.1126/science.abm3288	journal	October 2021
Cryo-EM structures of amyloid-β 42 filaments from human brains Yang, Yang; Arseni, Diana; Zhang, Wenjuan Science, Vol. 375, Issue 6577 https://doi.org/10.1126/science.abm7285	journal	January 2022
Blots on a field? Piller, Charles Science, Vol. 377, Issue 6604 https://doi.org/10.1126/science.add9993	journal	July 2022
Alzheimer’s target still viable but untested Ashe, Karen H. Science, Vol. 377, Issue 6609 https://doi.org/10.1126/science.ade4073	journal	August 2022
The amyloid-β oligomer Aβ*56 induces specific alterations in neuronal signaling that lead to tau phosphorylation and aggregation Amar, Fatou; Sherman, Mathew A.; Rush, Travis Science Signaling, Vol. 10, Issue 478 https://doi.org/10.1126/scisignal.aal2021	journal	May 2017
Beta-Amyloid Deposition in the Medial Temporal Lobe in Elderly Non-Demented Brains and in Alzheimer’s Disease Armstrong, R. A. Dementia and Geriatric Cognitive Disorders, Vol. 6, Issue 3 https://doi.org/10.1159/000106933	journal	January 1995
Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers Kayed, Rakez; Head, Elizabeth; Sarsoza, Floyd Molecular Neurodegeneration, Vol. 2, Issue 1 https://doi.org/10.1186/1750-1326-2-18	journal	January 2007
Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Aβ oligomers Kayed, Rakez; Canto, Isabel; Breydo, Leonid Molecular Neurodegeneration, Vol. 5, Issue 1 https://doi.org/10.1186/1750-1326-5-57	journal	January 2010
The neuropathological diagnosis of Alzheimer’s disease DeTure, Michael A.; Dickson, Dennis W. Molecular Neurodegeneration, Vol. 14, Issue 1 https://doi.org/10.1186/s13024-019-0333-5	journal	August 2019
Safety and tolerability of BAN2401 - a clinical study in Alzheimer’s disease with a protofibril selective Aβ antibody Logovinsky, Veronika; Satlin, Andrew; Lai, Robert Alzheimer's Research & Therapy, Vol. 8, Issue 1 https://doi.org/10.1186/s13195-016-0181-2	journal	April 2016
Aducanumab, gantenerumab, BAN2401, and ALZ-801—the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval Tolar, Martin; Abushakra, Susan; Hey, John A. Alzheimer's Research & Therapy, Vol. 12, Issue 1 https://doi.org/10.1186/s13195-020-00663-w	journal	August 2020
Lecanemab in patients with early Alzheimer’s disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study McDade, Eric; Cummings, Jeffrey L.; Dhadda, Shobha Alzheimer's Research & Therapy, Vol. 14, Issue 1 https://doi.org/10.1186/s13195-022-01124-2	journal	December 2022
Late-onset Alzheimer Disease Rabinovici, Gil D. CONTINUUM: Lifelong Learning in Neurology, Vol. 25, Issue 1 https://doi.org/10.1212/CON.0000000000000700	journal	February 2019
High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis Schindler, Suzanne E.; Bollinger, James G.; Ovod, Vitaliy Neurology https://doi.org/10.1212/WNL.0000000000008081	journal	August 2019
Risk Factors for Dementia in People With Down Syndrome: Issues in Assessment and Diagnosis Bush, Alick; Beail, Nigel American Journal on Mental Retardation, Vol. 109, Issue 2 https://doi.org/10.1352/0895-8017(2004)109<83:RFFDIP>2.0.CO;2	journal	January 2004
Intraneuronal beta-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation Oakley, H.; Cole, S. L.; Logan, S. Journal of Neuroscience, Vol. 26, Issue 40 https://doi.org/10.1523/JNEUROSCI.1202-06.2006	journal	October 2006
Large Soluble Oligomers of Amyloid β-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate Yang, Ting; Li, Shaomin; Xu, Huixin The Journal of Neuroscience, Vol. 37, Issue 1 https://doi.org/10.1523/JNEUROSCI.1698-16.2016	journal	November 2016
Soluble Conformers of Aβ and Tau Alter Selective Proteins Governing Axonal Transport Sherman, Mathew A.; LaCroix, Michael; Amar, Fatou The Journal of Neuroscience, Vol. 36, Issue 37 https://doi.org/10.1523/JNEUROSCI.1899-16.2016	journal	September 2016
Human Brain-Derived Aβ Oligomers Bind to Synapses and Disrupt Synaptic Activity in a Manner That Requires APP Wang, Zemin; Jackson, Rosemary J.; Hong, Wei The Journal of Neuroscience, Vol. 37, Issue 49 https://doi.org/10.1523/JNEUROSCI.2009-17.2017	journal	November 2017
Amyloid β-Protein Dimers Rapidly Form Stable Synaptotoxic Protofibrils O'Nuallain, Brian; Freir, Darragh B.; Nicoll, Andrew J. The Journal of Neuroscience, Vol. 30, Issue 43 https://doi.org/10.1523/JNEUROSCI.3537-10.2010	journal	October 2010
The amyloid hypothesis of Alzheimer's disease at 25 years Selkoe, Dennis J.; Hardy, John EMBO Molecular Medicine, Vol. 8, Issue 6 https://doi.org/10.15252/emmm.201606210	journal	March 2016
Aβ plaques Walker, Lary C. Free Neuropathology https://doi.org/10.17879/freeneuropathology-2020-3025	text	January 2020
Microvasculature in Brain Biopsy Specimens from Patients with Alzheimer's Disease: An Immunohistochemical and Ultrastructural Study Vinters, Harry V.; Secor, Diana Lenard; Read, Stephen L. Ultrastructural Pathology, Vol. 18, Issue 3 https://doi.org/10.3109/01913129409023202	journal	January 1994
The Murine Version of BAN2401 (mAb158) Selectively Reduces Amyloid-β Protofibrils in Brain and Cerebrospinal Fluid of tg-ArcSwe Mice Tucker, Stina; Möller, Christer; Tegerstedt, Karin Journal of Alzheimer's Disease, Vol. 43, Issue 2 https://doi.org/10.3233/JAD-140741	journal	November 2014
Non-Fibrillar Oligomeric Amyloid-β within Synapses Pickett, Eleanor K.; Koffie, Robert M.; Wegmann, Susanne Journal of Alzheimer's Disease, Vol. 53, Issue 3 https://doi.org/10.3233/JAD-160007	journal	August 2016
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade Cline, Erika N.; Bicca, Maíra Assunção; Viola, Kirsten L. Journal of Alzheimer's Disease, Vol. 64, Issue s1 https://doi.org/10.3233/JAD-179941	journal	June 2018
Alzheimer's Disease and the Amyloid-β Peptide Murphy, M. Paul; LeVine, Harry Journal of Alzheimer's Disease, Vol. 19, Issue 1 https://doi.org/10.3233/JAD-2010-1221	journal	January 2010
ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer’s Disease Krafft, Grant A.; Jerecic, Jasna; Siemers, Eric Frontiers in Neuroscience, Vol. 16 https://doi.org/10.3389/fnins.2022.848215	journal	April 2022
Massive antibody discovery used to probe structure–function relationships of the essential outer membrane protein LptD Storek, Kelly M.; Chan, Joyce; Vij, Rajesh eLife, Vol. 8 https://doi.org/10.7554/eLife.46258	journal	June 2019

Similar Records

Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril

Journal Article · Wed Jul 27 20:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1351799

Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin

Journal Article · Mon Dec 19 19:00:00 EST 2016 · Scientific Reports · OSTI ID:1624879

Design of non-aggregating variants of Aβ peptide

Journal Article · Fri Oct 24 00:00:00 EDT 2014 · Biochemical and Biophysical Research Communications · OSTI ID:22416797

Related Subjects

60 APPLIED LIFE SCIENCES
Biopolymers
Central nervous system
Chemistry
Nervous system diseases
Oligomers
Peptides and proteins

Antibodies Raised Against an Aβ Oligomer Mimic Recognize Pathological Features in Alzheimer’s Disease and Associated Amyloid-Disease Brain Tissue

Citation Formats

References (128)

Similar Records

Related Subjects