{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:17:00Z","timestamp":1789193820847,"version":"build-2803163510"},"reference-count":129,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":65,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG056569"],"award-info":[{"award-number":["R01AG056569"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["RF1AG094856"],"award-info":[{"award-number":["RF1AG094856"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM150196"],"award-info":[{"award-number":["R01GM150196"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-026-73075-3","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T02:56:05Z","timestamp":1778554565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["\u03b1\/Sulfonyl-\u03b3-AApeptide foldamers mitigate Alzheimer\u2019s disease pathology by stabilizing transient helical domains in A\u03b2"],"prefix":"10.1038","volume":"17","author":[{"given":"Heng","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8836-601X","authenticated-orcid":false,"given":"Firoz","family":"Akhter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Akhter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9686-2072","authenticated-orcid":false,"given":"Xudong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Calcul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanhai","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0818-2972","authenticated-orcid":false,"given":"Libin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3057-1889","authenticated-orcid":false,"given":"Donghui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3106-3306","authenticated-orcid":false,"given":"Jianfeng","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"73075_CR1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nrm2101","volume":"8","author":"C Haass","year":"2007","unstructured":"Haass, C. & Selkoe, D. J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer\u2019s amyloid beta-peptide. Nat. Rev. Mol. Cell. Biol. 8, 101\u2013112 (2007).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"73075_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nm.4269","volume":"23","author":"YC Wong","year":"2017","unstructured":"Wong, Y. C. & Krainc, D. alpha-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies. Nat. Med. 23, 1\u201313 (2017).","journal-title":"Nat. Med."},{"key":"73075_CR3","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.molmed.2015.04.005","volume":"21","author":"A Mukherjee","year":"2015","unstructured":"Mukherjee, A., Morales-Scheihing, D., Butler, P. C. & Soto, C. Type 2 diabetes as a protein misfolding disease. Trends Mol. Med. 21, 439\u2013449 (2015).","journal-title":"Trends Mol. Med."},{"key":"73075_CR4","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nchembio.546","volume":"7","author":"J Xu","year":"2011","unstructured":"Xu, J. et al. Gain of function of mutant p53 by coaggregation with multiple tumor suppressors. Nat. Chem. Biol. 7, 285\u2013295 (2011).","journal-title":"Nat. Chem. Biol."},{"key":"73075_CR5","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1002\/ana.410270502","volume":"27","author":"ST DeKosky","year":"1990","unstructured":"DeKosky, S. T. & Scheff, S. W. Synapse loss in frontal cortex biopsies in Alzheimer\u2019s disease: correlation with cognitive severity. Ann. Neurol. 27, 457\u2013464 (1990).","journal-title":"Ann. Neurol."},{"key":"73075_CR6","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1126\/science.aag2590","volume":"353","author":"RM Ransohoff","year":"2016","unstructured":"Ransohoff, R. M. How neuroinflammation contributes to neurodegeneration. Science 353, 777\u2013783 (2016).","journal-title":"Science"},{"key":"73075_CR7","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1007\/s13311-019-00755-y","volume":"16","author":"JC Ryu","year":"2019","unstructured":"Ryu, J. C., Zimmer, E. R., Rosa-Neto, P. & Yoon, S. O. Consequences of metabolic disruption in Alzheimer\u2019s disease pathology. Neurotherapeutics 16, 600\u2013610 (2019).","journal-title":"Neurotherapeutics"},{"key":"73075_CR8","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1126\/science.1162844","volume":"321","author":"MA Busche","year":"2008","unstructured":"Busche, M. A. et al. Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer\u2019s disease. Science 321, 1686\u20131689 (2008).","journal-title":"Science"},{"key":"73075_CR9","doi-asserted-by":"publisher","first-page":"165","DOI":"10.3233\/JAD-191236","volume":"76","author":"F Akhter","year":"2020","unstructured":"Akhter, F. et al. High dietary advanced glycation end products impair mitochondrial and cognitive function. J. Alzheimers Dis. 76, 165\u2013178 (2020).","journal-title":"J. Alzheimers Dis."},{"key":"73075_CR10","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1093\/brain\/awae229","volume":"148","author":"S Samanta","year":"2025","unstructured":"Samanta, S. et al. Synaptic mitochondria glycation contributes to mitochondrial stress and cognitive dysfunction. Brain 148, 262\u2013275 (2025).","journal-title":"Brain"},{"key":"73075_CR11","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.freeradbiomed.2020.12.021","volume":"164","author":"F Akhter","year":"2021","unstructured":"Akhter, F., Chen, D., Akhter, A., Yan, S. F. & Yan, S. S. Age-dependent accumulation of dicarbonyls and advanced glycation endproducts (AGEs) associates with mitochondrial stress. Free Radic. Biol. Med. 164, 429\u2013438 (2021).","journal-title":"Free Radic. Biol. Med."},{"key":"73075_CR12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2505046122","volume":"122","author":"F Akhter","year":"2025","unstructured":"Akhter, F. et al. Amyloid-beta glycation induces neuronal mitochondrial dysfunction and Alzheimer\u2019s pathogenesis via VDAC1-dependent mtDNA efflux. Proc. Natl. Acad. Sci. USA. 122, e2505046122 (2025).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73075_CR13","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1002\/ana.410300410","volume":"30","author":"RD Terry","year":"1991","unstructured":"Terry, R. D. et al. Physical basis of cognitive alterations in Alzheimer\u2019s disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30, 572\u2013580 (1991).","journal-title":"Ann. Neurol."},{"key":"73075_CR14","doi-asserted-by":"publisher","first-page":"3228","DOI":"10.1073\/pnas.96.6.3228","volume":"96","author":"AY Hsia","year":"1999","unstructured":"Hsia, A. Y. et al. Plaque-independent disruption of neural circuits in Alzheimer\u2019s disease mouse models. Proc. Natl. Acad. Sci. USA 96, 3228\u20133233 (1999).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73075_CR15","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/416535a","volume":"416","author":"DM Walsh","year":"2002","unstructured":"Walsh, D. M. et al. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535\u2013539 (2002).","journal-title":"Nature"},{"key":"73075_CR16","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.neuron.2006.10.035","volume":"52","author":"H Hsieh","year":"2006","unstructured":"Hsieh, H. et al. AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 52, 831\u2013843 (2006).","journal-title":"Neuron"},{"key":"73075_CR17","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1093\/brain\/awad432","volume":"147","author":"S Samanta","year":"2023","unstructured":"Samanta, S. et al. New cyclophilin D inhibitor rescues mitochondrial and cognitive function in Alzheimer\u2019s disease. Brain 147, 1710\u20131725 (2023).","journal-title":"Brain"},{"key":"73075_CR18","doi-asserted-by":"publisher","first-page":"600084","DOI":"10.3389\/fnmol.2020.600084","volume":"13","author":"A Hector","year":"2020","unstructured":"Hector, A. & Brouillette, J. Hyperactivity induced by soluble amyloid-beta oligomers in the early stages of Alzheimer\u2019s disease. Front Mol. Neurosci. 13, 600084 (2020).","journal-title":"Front Mol. Neurosci."},{"key":"73075_CR19","doi-asserted-by":"publisher","first-page":"19318","DOI":"10.1073\/pnas.0804871105","volume":"105","author":"X Wang","year":"2008","unstructured":"Wang, X. et al. Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission\/fusion proteins. Proc. Natl. Acad. Sci. USA. 105, 19318\u201319323 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73075_CR20","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","volume":"14","author":"MT Heneka","year":"2015","unstructured":"Heneka, M. T. et al. Neuroinflammation in Alzheimer\u2019s disease. Lancet Neurol. 14, 388\u2013405 (2015).","journal-title":"Lancet Neurol."},{"key":"73075_CR21","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy, J. & Selkoe, D. J. The amyloid hypothesis of Alzheimer\u2019s disease: progress and problems on the road to therapeutics. Science 297, 353\u2013356 (2002).","journal-title":"Science"},{"key":"73075_CR22","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nrn.2016.13","volume":"17","author":"DM Walsh","year":"2016","unstructured":"Walsh, D. M. & Selkoe, D. J. A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration. Nat. Rev. Neurosci. 17, 251\u2013260 (2016).","journal-title":"Nat. Rev. Neurosci."},{"key":"73075_CR23","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/s41392-022-01157-x","volume":"7","author":"X Liu","year":"2022","unstructured":"Liu, X. et al. Clusterin transduces Alzheimer-risk signals to amyloidogenesis. Signal. Transduct. Target Ther. 7, 325 (2022).","journal-title":"Signal. Transduct. Target Ther."},{"key":"73075_CR24","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/nrneurol.2009.219","volume":"6","author":"CA Lemere","year":"2010","unstructured":"Lemere, C. A. & Masliah, E. Can Alzheimer disease be prevented by amyloid-beta immunotherapy? Nat. Rev. Neurol. 6, 108\u2013119 (2010).","journal-title":"Nat. Rev. Neurol."},{"key":"73075_CR25","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/j.1747-0285.2005.00318.x","volume":"67","author":"Y Porat","year":"2006","unstructured":"Porat, Y., Abramowitz, A. & Gazit, E. Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism. Chem. Biol. Drug Des. 67, 27\u201337 (2006).","journal-title":"Chem. Biol. Drug Des."},{"key":"73075_CR26","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1146\/annurev.biochem.75.101304.123901","volume":"75","author":"F Chiti","year":"2006","unstructured":"Chiti, F. & Dobson, C. M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75, 333\u2013366 (2006).","journal-title":"Annu. Rev. Biochem."},{"key":"73075_CR27","doi-asserted-by":"publisher","first-page":"10378","DOI":"10.1002\/anie.201302840","volume":"52","author":"LM Yan","year":"2013","unstructured":"Yan, L. M. et al. Selectively N-methylated soluble IAPP mimics as potent IAPP receptor agonists and nanomolar inhibitors of cytotoxic self-assembly of both IAPP and Abeta40. Angew. Chem. Int. Ed. Engl. 52, 10378\u201310383 (2013).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"73075_CR28","doi-asserted-by":"publisher","first-page":"13882","DOI":"10.1021\/jacs.6b06000","volume":"138","author":"NL Truex","year":"2016","unstructured":"Truex, N. L., Wang, Y. & Nowick, J. S. Assembly of peptides derived from beta-sheet regions of beta-amyloid. J. Am. Chem. Soc. 138, 13882\u201313890 (2016).","journal-title":"J. Am. Chem. Soc."},{"key":"73075_CR29","doi-asserted-by":"publisher","first-page":"203","DOI":"10.25100\/cm.v47i4.2640","volume":"47","author":"A Barrera-Ocampo","year":"2016","unstructured":"Barrera-Ocampo, A. & Lopera, F. Amyloid-beta immunotherapy: the hope for Alzheimer disease? Colomb. Med. 47, 203\u2013212 (2016).","journal-title":"Colomb. Med."},{"key":"73075_CR30","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s40259-023-00633-2","volume":"38","author":"J Cummings","year":"2024","unstructured":"Cummings, J., Osse, A. M. L., Cammann, D., Powell, J. & Chen, J. Anti-amyloid monoclonal antibodies for the treatment of Alzheimer\u2019s disease. BioDrugs 38, 5\u201322 (2024).","journal-title":"BioDrugs"},{"key":"73075_CR31","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/nsmb.2971","volume":"22","author":"SIA Cohen","year":"2015","unstructured":"Cohen, S. I. A. et al. A molecular chaperone breaks the catalytic cycle that generates toxic Abeta oligomers. Nat. Struct. Mol. Biol. 22, 207\u2013213 (2015).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"73075_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10948","volume":"7","author":"P Arosio","year":"2016","unstructured":"Arosio, P. et al. Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation. Nat. Commun. 7, 10948 (2016).","journal-title":"Nat. Commun."},{"key":"73075_CR33","unstructured":"Jokar, S., et al. Recent advances in the design and applications of amyloid-beta peptide aggregation inhibitors for Alzheimer\u2019s disease therapy. Biophys. Rev. 30, 373\u2013398 (2019)."},{"key":"73075_CR34","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1021\/acsmedchemlett.9b00039","volume":"10","author":"ML Bolognesi","year":"2019","unstructured":"Bolognesi, M. L. Harnessing polypharmacology with medicinal chemistry. ACS Med. Chem. Lett. 10, 273\u2013275 (2019).","journal-title":"ACS Med. Chem. Lett."},{"key":"73075_CR35","doi-asserted-by":"publisher","first-page":"117838","DOI":"10.1016\/j.ejmech.2025.117838","volume":"296","author":"A Santini","year":"2025","unstructured":"Santini, A. et al. AR-A014418-based dual glycogen synthase kinase 3beta\/histone deacetylase inhibitors as potential therapeutics for Alzheimer\u2019s disease. Eur. J. Med. Chem. 296, 117838 (2025).","journal-title":"Eur. J. Med. Chem."},{"key":"73075_CR36","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.nurt.2008.10.042","volume":"6","author":"ML Bolognesi","year":"2009","unstructured":"Bolognesi, M. L., Cavalli, A. & Melchiorre, C. Memoquin: a multi-target-directed ligand as an innovative therapeutic opportunity for Alzheimer\u2019s disease. Neurotherapeutics 6, 152\u2013162 (2009).","journal-title":"Neurotherapeutics"},{"key":"73075_CR37","doi-asserted-by":"publisher","first-page":"483","DOI":"10.2174\/138945012799499794","volume":"13","author":"O Weinreb","year":"2012","unstructured":"Weinreb, O., Amit, T., Bar-Am, O. & Youdim, M. B. Ladostigil: a novel multimodal neuroprotective drug with cholinesterase and brain-selective monoamine oxidase inhibitory activities for Alzheimer\u2019s disease treatment. Curr. Drug Targets 13, 483\u2013494 (2012).","journal-title":"Curr. Drug Targets"},{"key":"73075_CR38","doi-asserted-by":"publisher","first-page":"116070","DOI":"10.1016\/j.ejmech.2023.116070","volume":"265","author":"WB Zang","year":"2024","unstructured":"Zang, W. B. et al. Curcumin hybrid molecules for the treatment of Alzheimer\u2019s disease: structure and pharmacological activities. Eur. J. Med. Chem. 265, 116070 (2024).","journal-title":"Eur. J. Med. Chem."},{"key":"73075_CR39","doi-asserted-by":"publisher","first-page":"9191","DOI":"10.1073\/pnas.0810364106","volume":"106","author":"C Nerelius","year":"2009","unstructured":"Nerelius, C. et al. Alpha-helix targeting reduces amyloid-beta peptide toxicity. Proc. Natl. Acad. Sci. USA. 106, 9191\u20139196 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73075_CR40","doi-asserted-by":"publisher","first-page":"17098","DOI":"10.1021\/jacs.7b08259","volume":"139","author":"S Kumar","year":"2017","unstructured":"Kumar, S., Henning-Knechtel, A., Chehade, I., Magzoub, M. & Hamilton, A. D. Foldamer-mediated structural rearrangement attenuates abeta oligomerization and cytotoxicity. J. Am. Chem. Soc. 139, 17098\u201317108 (2017).","journal-title":"J. Am. Chem. Soc."},{"key":"73075_CR41","doi-asserted-by":"crossref","unstructured":"Hamilton, A. D. Peptidomimetic-based multidomain targeting offers critical evaluation of A\u03b2 structure and toxic function. J. Am. Chem. Soc. 140, 6562\u20136574 (2018).","DOI":"10.1021\/jacs.7b13401"},{"key":"73075_CR42","doi-asserted-by":"crossref","unstructured":"Hamilton, S.K.a.A.D. \u03b1\u2011helix mimetics as modulators of A\u03b2 self-assembly. J. Am. Chem. Soc. 139, 5744\u20135755 (2017).","DOI":"10.1021\/jacs.6b09734"},{"key":"73075_CR43","doi-asserted-by":"publisher","first-page":"14612","DOI":"10.1002\/chem.202001716","volume":"26","author":"J Kaffy","year":"2020","unstructured":"Kaffy, J. et al. Helical gamma-peptide foldamers as dual inhibitors of amyloid-beta peptide and islet amyloid polypeptide oligomerization and fibrillization. Chemistry 26, 14612\u201314622 (2020).","journal-title":"Chemistry"},{"key":"73075_CR44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2311733121","volume":"121","author":"H Liu","year":"2024","unstructured":"Liu, H. et al. Helical sulfonyl-gamma-AApeptides modulating Abeta oligomerization and cytotoxicity by recognizing Abeta helix. Proc. Natl. Acad. Sci. USA. 121, e2311733121 (2024).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73075_CR45","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1021\/acs.accounts.5b00492","volume":"49","author":"Y Shi","year":"2016","unstructured":"Shi, Y. et al. gamma-AApeptides: design, structure, and applications. Acc. Chem. Res. 49, 428\u2013441 (2016).","journal-title":"Acc. Chem. Res."},{"key":"73075_CR46","doi-asserted-by":"publisher","first-page":"9916","DOI":"10.1002\/anie.201805184","volume":"57","author":"F She","year":"2018","unstructured":"She, F. et al. De Novo left-handed synthetic peptidomimetic foldamers. Angew. Chem. Int. Ed. Engl. 57, 9916\u20139920 (2018).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"73075_CR47","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1021\/acs.accounts.0c00482","volume":"53","author":"P Sang","year":"2020","unstructured":"Sang, P. et al. Sulfono-gamma-AApeptides as helical mimetics: crystal structures and applications. Acc. Chem. Res. 53, 2425\u20132442 (2020).","journal-title":"Acc. Chem. Res."},{"key":"73075_CR48","doi-asserted-by":"publisher","first-page":"9290","DOI":"10.1021\/acs.jmedchem.7b01280","volume":"60","author":"Y Shi","year":"2017","unstructured":"Shi, Y. et al. One-bead-two-compound thioether bridged macrocyclic gamma-AApeptide screening library against EphA2. J. Med. Chem. 60, 9290\u20139298 (2017).","journal-title":"J. Med. Chem."},{"key":"73075_CR49","doi-asserted-by":"publisher","first-page":"10757","DOI":"10.1073\/pnas.1819663116","volume":"116","author":"P Sang","year":"2019","unstructured":"Sang, P. et al. Inhibition of beta-catenin\/B cell lymphoma 9 protein-protein interaction using alpha-helix-mimicking sulfono-gamma-AApeptide inhibitors. Proc. Natl. Acad. Sci. USA. 116, 10757\u201310762 (2019).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73075_CR50","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1021\/acs.jmedchem.9b00993","volume":"63","author":"P Sang","year":"2020","unstructured":"Sang, P. et al. alpha-helix-mimicking sulfono-gamma-AApeptide inhibitors for p53-MDM2\/MDMX protein-protein interactions. J. Med. Chem. 63, 975\u2013986 (2020).","journal-title":"J. Med. Chem."},{"key":"73075_CR51","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz4988","volume":"6","author":"P Sang","year":"2020","unstructured":"Sang, P. et al. The activity of sulfono-gamma-AApeptide helical foldamers that mimic GLP-1. Sci. Adv. 6, eaaz4988 (2020).","journal-title":"Sci. Adv."},{"key":"73075_CR52","doi-asserted-by":"publisher","first-page":"13187","DOI":"10.1021\/acs.jmedchem.0c01638","volume":"63","author":"Y Shi","year":"2020","unstructured":"Shi, Y. et al. Rational design of right-handed heterogeneous peptidomimetics as inhibitors of protein-protein interactions. J. Med. Chem. 63, 13187\u201313196 (2020).","journal-title":"J. Med. Chem."},{"key":"73075_CR53","doi-asserted-by":"publisher","first-page":"11219","DOI":"10.1021\/acs.jmedchem.1c00607","volume":"64","author":"M Zheng","year":"2021","unstructured":"Zheng, M. et al. Discovery of cyclic peptidomimetic ligands targeting the extracellular domain of EGFR. J. Med. Chem. 64, 11219\u201311228 (2021).","journal-title":"J. Med. Chem."},{"key":"73075_CR54","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1021\/jacs.1c09571","volume":"144","author":"S Abdulkadir","year":"2022","unstructured":"Abdulkadir, S. et al. Modulating angiogenesis by proteomimetics of vascular endothelial growth factor. J. Am. Chem. Soc. 144, 270\u2013281 (2022).","journal-title":"J. Am. Chem. Soc."},{"key":"73075_CR55","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1021\/acs.jmedchem.1c01922","volume":"65","author":"B Huang","year":"2022","unstructured":"Huang, B. et al. Activation of E6AP\/UBE3A-mediated protein ubiquitination and degradation pathways by a cyclic gamma-AA peptide. J. Med. Chem. 65, 2497\u20132506 (2022).","journal-title":"J. Med. Chem."},{"key":"73075_CR56","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41421-022-00455-6","volume":"8","author":"S Xue","year":"2022","unstructured":"Xue, S. et al. A novel cyclic gamma-AApeptide-based long-acting pan-coronavirus fusion inhibitor with potential oral bioavailability by targeting two sites in spike protein. Cell Discov. 8, 88 (2022).","journal-title":"Cell Discov."},{"key":"73075_CR57","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1021\/acs.jmedchem.2c01459","volume":"66","author":"L Zhou","year":"2023","unstructured":"Zhou, L. et al. Inhibition of the ubiquitin transfer cascade by a peptidomimetic foldamer mimicking the E2 N-terminal helix. J. Med. Chem. 66, 491\u2013502 (2023).","journal-title":"J. Med. Chem."},{"key":"73075_CR58","doi-asserted-by":"publisher","first-page":"5661","DOI":"10.1021\/jacs.7b11997","volume":"140","author":"P Teng","year":"2018","unstructured":"Teng, P. et al. Hydrogen-bonding-driven 3D supramolecular assembly of peptidomimetic zipper. J. Am. Chem. Soc. 140, 5661\u20135665 (2018).","journal-title":"J. Am. Chem. Soc."},{"key":"73075_CR59","doi-asserted-by":"publisher","first-page":"7778","DOI":"10.1002\/anie.201903259","volume":"58","author":"P Teng","year":"2019","unstructured":"Teng, P. et al. Orthogonal halogen-bonding-driven 3D supramolecular assembly of right-handed synthetic helical peptides. Angew. Chem. Int. Ed. Engl. 58, 7778\u20137782 (2019).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"73075_CR60","doi-asserted-by":"publisher","first-page":"5930","DOI":"10.1046\/j.0014-2956.2001.02537.x","volume":"268","author":"R Riek","year":"2001","unstructured":"Riek, R., Guntert, P., Dobeli, H., Wipf, B. & Wuthrich, K. NMR studies in aqueous solution fail to identify significant conformational differences between the monomeric forms of two Alzheimer peptides with widely different plaque-competence, A beta(1-40)(ox) and A beta(1-42)(ox). Eur. J. Biochem. 268, 5930\u20135936 (2001).","journal-title":"Eur. J. Biochem."},{"key":"73075_CR61","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.jmb.2006.09.046","volume":"364","author":"Y Yan","year":"2006","unstructured":"Yan, Y. & Wang, C. Abeta42 is more rigid than Abeta40 at the C terminus: implications for Abeta aggregation and toxicity. J. Mol. Biol. 364, 853\u2013862 (2006).","journal-title":"J. Mol. Biol."},{"key":"73075_CR62","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s10858-007-9176-4","volume":"39","author":"J Jarvet","year":"2007","unstructured":"Jarvet, J., Danielsson, J., Damberg, P., Oleszczuk, M. & Graslund, A. Positioning of the Alzheimer Abeta(1-40) peptide in SDS micelles using NMR and paramagnetic probes. J. Biomol. NMR 39, 63\u201372 (2007).","journal-title":"J. Biomol. NMR"},{"key":"73075_CR63","doi-asserted-by":"publisher","first-page":"11064","DOI":"10.1021\/bi972979f","volume":"37","author":"M Coles","year":"1998","unstructured":"Coles, M., Bicknell, W., Watson, A. A., Fairlie, D. P. & Craik, D. J. Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is? Biochemistry 37, 11064\u201311077 (1998).","journal-title":"Biochemistry"},{"key":"73075_CR64","doi-asserted-by":"publisher","first-page":"6562","DOI":"10.1021\/jacs.7b13401","volume":"140","author":"S Kumar","year":"2018","unstructured":"Kumar, S., Henning-Knechtel, A., Magzoub, M. & Hamilton, A. D. Peptidomimetic-based multidomain targeting offers critical evaluation of abeta structure and toxic function. J. Am. Chem. Soc. 140, 6562\u20136574 (2018).","journal-title":"J. Am. Chem. Soc."},{"key":"73075_CR65","doi-asserted-by":"publisher","first-page":"5744","DOI":"10.1021\/jacs.6b09734","volume":"139","author":"S Kumar","year":"2017","unstructured":"Kumar, S. & Hamilton, A. D. alpha-helix mimetics as modulators of abeta self-assembly. J. Am. Chem. Soc. 139, 5744\u20135755 (2017).","journal-title":"J. Am. Chem. Soc."},{"key":"73075_CR66","doi-asserted-by":"publisher","first-page":"28176","DOI":"10.1074\/jbc.M803159200","volume":"283","author":"A Jan","year":"2008","unstructured":"Jan, A., Gokce, O., Luthi-Carter, R. & Lashuel, H. A. The ratio of monomeric to aggregated forms of Abeta40 and Abeta42 is an important determinant of amyloid-beta aggregation, fibrillogenesis, and toxicity. J. Biol. Chem. 283, 28176\u201328189 (2008).","journal-title":"J. Biol. Chem."},{"key":"73075_CR67","doi-asserted-by":"publisher","first-page":"e1003537","DOI":"10.1371\/journal.ppat.1003537","volume":"9","author":"R Morales","year":"2013","unstructured":"Morales, R., Moreno-Gonzalez, I. & Soto, C. Cross-seeding of misfolded proteins: implications for etiology and pathogenesis of protein misfolding diseases. PLoS Pathog. 9, e1003537 (2013).","journal-title":"PLoS Pathog."},{"key":"73075_CR68","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1002\/anie.200904902","volume":"49","author":"E Andreetto","year":"2010","unstructured":"Andreetto, E. et al. Identification of hot regions of the Abeta-IAPP interaction interface as high-affinity binding sites in both cross- and self-association. Angew. Chem. Int. Ed. Engl. 49, 3081\u20133085 (2010).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"73075_CR69","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1002\/cbic.200700427","volume":"8","author":"M Bartolini","year":"2007","unstructured":"Bartolini, M. et al. Insight into the kinetic of amyloid beta (1-42) peptide self-aggregation: elucidation of inhibitors\u2019 mechanism of action. Chembiochem 8, 2152\u20132161 (2007).","journal-title":"Chembiochem"},{"key":"73075_CR70","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s13361-016-1545-3","volume":"28","author":"AC Leney","year":"2017","unstructured":"Leney, A. C. & Heck, A. J. Native mass spectrometry: what is in the name? J. Am. Soc. Mass Spectrom. 28, 5\u201313 (2017).","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"73075_CR71","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","volume":"8","author":"Y Zhang","year":"2023","unstructured":"Zhang, Y., Chen, H., Li, R., Sterling, K. & Song, W. Amyloid beta-based therapy for Alzheimer\u2019s disease: challenges, successes and future. Signal Transduct. Target Ther. 8, 248 (2023).","journal-title":"Signal Transduct. Target Ther."},{"key":"73075_CR72","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1146\/annurev.biochem.66.1.385","volume":"66","author":"JD Harper","year":"1997","unstructured":"Harper, J. D. & Lansbury, P. T. Jr Models of amyloid seeding in Alzheimer\u2019s disease and scrapie: mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. Annu. Rev. Biochem. 66, 385\u2013407 (1997).","journal-title":"Annu. Rev. Biochem."},{"key":"73075_CR73","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2206240119","volume":"119","author":"KA Murray","year":"2022","unstructured":"Murray, K. A. et al. De novo designed protein inhibitors of amyloid aggregation and seeding. Proc. Natl. Acad. Sci. USA. 119, e2206240119 (2022).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73075_CR74","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/39522","volume":"389","author":"SD Yan","year":"1997","unstructured":"Yan, S. D. et al. An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer\u2019s disease. Nature 389, 689\u2013695 (1997).","journal-title":"Nature"},{"key":"73075_CR75","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1074\/jbc.274.4.2145","volume":"274","author":"SD Yan","year":"1999","unstructured":"Yan, S. D. et al. Role of ERAB\/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity. J. Biol. Chem. 274, 2145\u20132156 (1999).","journal-title":"J. Biol. Chem."},{"key":"73075_CR76","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/alzrt272","volume":"6","author":"WF Goure","year":"2014","unstructured":"Goure, W. F., Krafft, G. A., Jerecic, J. & Hefti, F. Targeting the proper amyloid-beta neuronal toxins: a path forward for Alzheimer\u2019s disease immunotherapeutics. Alz. Res. Ther. 6, 42 (2014).","journal-title":"Alz. Res. Ther."},{"key":"73075_CR77","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/sj.cdd.4401528","volume":"12","author":"H Kadowaki","year":"2005","unstructured":"Kadowaki, H. et al. Amyloid \u03b2 induces neuronal cell death through ROS-mediated ASK1 activation. Cell Death Differ. 12, 19\u201324 (2005).","journal-title":"Cell Death Differ."},{"key":"73075_CR78","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.neuroscience.2007.06.036","volume":"149","author":"LA Glantz","year":"2007","unstructured":"Glantz, L. A., Gilmore, J. H., Hamer, R. M., Lieberman, J. A. & Jarskog, L. F. Synaptophysin and postsynaptic density protein 95 in the human prefrontal cortex from mid-gestation into early adulthood. Neuroscience 149, 582\u2013591 (2007).","journal-title":"Neuroscience"},{"key":"73075_CR79","doi-asserted-by":"publisher","first-page":"4012","DOI":"10.1073\/pnas.0811698106","volume":"106","author":"RM Koffie","year":"2009","unstructured":"Koffie, R. M. et al. Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc. Natl. Acad. Sci. USA. 106, 4012\u20134017 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"73075_CR80","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40968-6","volume":"14","author":"MM Novakovic","year":"2023","unstructured":"Novakovic, M. M. et al. Astrocyte reactivity and inflammation-induced depression-like behaviors are regulated by Orai1 calcium channels. Nat. Commun. 14, 5500 (2023).","journal-title":"Nat. Commun."},{"key":"73075_CR81","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0871-0","volume":"14","author":"KS Kirkley","year":"2017","unstructured":"Kirkley, K. S., Popichak, K. A., Afzali, M. F., Legare, M. E. & Tjalkens, R. B. Microglia amplify inflammatory activation of astrocytes in manganese neurotoxicity. J. Neuroinflamm. 14, 99 (2017).","journal-title":"J. Neuroinflamm."},{"key":"73075_CR82","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","volume":"8","author":"Y Zhang","year":"2023","unstructured":"Zhang, Y., Chen, H., Li, R., Sterling, K. & Song, W. Amyloid \u03b2-based therapy for Alzheimer\u2019s disease: challenges, successes and future. Signal Trans. Target. Ther. 8, 248 (2023).","journal-title":"Signal Trans. Target. Ther."},{"key":"73075_CR83","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16074-2","volume":"11","author":"M Calvo-Rodriguez","year":"2020","unstructured":"Calvo-Rodriguez, M. et al. Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer\u2019s disease. Nat. Commun. 11, 2146 (2020).","journal-title":"Nat. Commun."},{"key":"73075_CR84","doi-asserted-by":"publisher","first-page":"S107","DOI":"10.3233\/JAD-179921","volume":"64","author":"CX Gong","year":"2018","unstructured":"Gong, C. X., Liu, F. & Iqbal, K. Multifactorial hypothesis and multi-targets for Alzheimer\u2019s disease. J. Alzheimers Dis. 64, S107\u2013S117 (2018).","journal-title":"J. Alzheimers Dis."},{"key":"73075_CR85","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.bbadis.2009.10.006","volume":"1802","author":"PI Moreira","year":"2010","unstructured":"Moreira, P. I., Carvalho, C., Zhu, X., Smith, M. A. & Perry, G. Mitochondrial dysfunction is a trigger of Alzheimer\u2019s disease pathophysiology. Biochim. Biophys. Acta 1802, 2\u201310 (2010).","journal-title":"Biochim. Biophys. Acta"},{"key":"73075_CR86","doi-asserted-by":"crossref","unstructured":"Akhter, F., et al. Amyloid beta glycation leads to 1 neuronal mitochondrial dysfunction and Alzheimer\u2019s pathogenesis through VDAC1-dependent mtDNA efflux. bioRxiv, 2024.2005.2014.594173 (2024).","DOI":"10.1101\/2024.05.14.594173"},{"key":"73075_CR87","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/978-1-4939-7816-8_25","volume":"1779","author":"SF Yan","year":"2018","unstructured":"Yan, S. F., Akhter, F., Sosunov, A. A. & Yan, S. S. Identification and characterization of amyloid-\u03b2 accumulation in synaptic mitochondria. Methods Mol. Biol. 1779, 415\u2013433 (2018).","journal-title":"Methods Mol. Biol."},{"key":"73075_CR88","doi-asserted-by":"crossref","unstructured":"Akhter, F., et al. RAGE exacerbate amyloid beta (A\u03b2) induced Alzheimer pathology: a systemic overview. in Networking of Mutagens in Environmental Toxicology (ed. Kesari, K. K.) 159-170 (Springer International Publishing, 2019).","DOI":"10.1007\/978-3-319-96511-6_9"},{"key":"73075_CR89","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1002\/ana.22313","volume":"69","author":"D Puzzo","year":"2011","unstructured":"Puzzo, D. et al. Endogenous amyloid-\u03b2 is necessary for hippocampal synaptic plasticity and memory. Ann. Neurol. 69, 819\u2013830 (2011).","journal-title":"Ann. Neurol."},{"key":"73075_CR90","doi-asserted-by":"publisher","first-page":"19377","DOI":"10.1074\/jbc.M111.321448","volume":"287","author":"N Nunes-Tavares","year":"2012","unstructured":"Nunes-Tavares, N. et al. Inhibition of choline acetyltransferase as a mechanism for cholinergic dysfunction induced by amyloid-\u03b2 peptide oligomers. J. Biol. Chem. 287, 19377\u201319385 (2012).","journal-title":"J. Biol. Chem."},{"key":"73075_CR91","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2219994120","volume":"120","author":"X-K Yang","year":"2023","unstructured":"Yang, X.-K. et al. Nanoelectrochemistry reveals how soluble A\u03b242 oligomers alter vesicular storage and release of glutamate. Proc. Natl. Acad. Sci. USA. 120, e2219994120 (2023).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"73075_CR92","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1038\/s41380-021-01384-8","volume":"27","author":"N Huber","year":"2022","unstructured":"Huber, N. et al. Deficient neurotransmitter systems and synaptic function in frontotemporal lobar degeneration\u2014Insights into disease mechanisms and current therapeutic approaches. Mol. Psychiatry 27, 1300\u20131309 (2022).","journal-title":"Mol. Psychiatry"},{"key":"73075_CR93","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/978-94-017-7215-0_9","volume":"867","author":"MA Isgr\u00f2","year":"2015","unstructured":"Isgr\u00f2, M. A., Bottoni, P. & Scatena, R. Neuron-specific enolase as a biomarker: biochemical and clinical aspects. Adv. Exp. Med. Biol. 867, 125\u2013143 (2015).","journal-title":"Adv. Exp. Med. Biol."},{"key":"73075_CR94","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13578-024-01240-6","volume":"14","author":"S Horvat","year":"2024","unstructured":"Horvat, S., Kos, J. & Pi\u0161lar, A. Multifunctional roles of \u03b3-enolase in the central nervous system: more than a neuronal marker. Cell Biosci. 14, 61 (2024).","journal-title":"Cell Biosci."},{"key":"73075_CR95","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","volume":"14","author":"M Khalil","year":"2018","unstructured":"Khalil, M. et al. Neurofilaments as biomarkers in neurological disorders. Nat. Rev. Neurol. 14, 577\u2013589 (2018).","journal-title":"Nat. Rev. Neurol."},{"key":"73075_CR96","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","volume":"388","author":"CH van Dyck","year":"2023","unstructured":"van Dyck, C. H. et al. Lecanemab in early Alzheimer\u2019s disease. N. Engl. J. Med. 388, 9\u201321 (2023).","journal-title":"N. Engl. J. Med."},{"key":"73075_CR97","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1001\/jama.2023.13239","volume":"330","author":"JR Sims","year":"2023","unstructured":"Sims, J. R. et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 330, 512\u2013527 (2023).","journal-title":"JAMA"},{"key":"73075_CR98","first-page":"407","volume":"64","author":"JA Hey","year":"2025","unstructured":"Hey, J. A. et al. Clinical pharmacokinetics of Oral ALZ-801\/valiltramiprosate in a 2-Year phase 2 trial of APOE4 carriers with early Alzheimer\u2019s disease. Clin. Pharmacokinet. 64, 407\u2013424 (2025).","journal-title":"Clin. Pharmacokinet."},{"key":"73075_CR99","doi-asserted-by":"publisher","first-page":"6032","DOI":"10.2174\/0109298673264076230921065945","volume":"31","author":"S Kumar","year":"2024","unstructured":"Kumar, S., Mahajan, A., Ambatwar, R. & Khatik, G. L. Recent advancements in the treatment of Alzheimer\u2019s disease: a multitarget-directed ligand approach. Curr. Med. Chem. 31, 6032\u20136062 (2024).","journal-title":"Curr. Med. Chem."},{"key":"73075_CR100","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adi2245","volume":"16","author":"SJ Barker","year":"2024","unstructured":"Barker, S. J. et al. Targeting the transferrin receptor to transport antisense oligonucleotides across the mammalian blood-brain barrier. Sci. Transl. Med. 16, eadi2245 (2024).","journal-title":"Sci. Transl. Med."},{"key":"73075_CR101","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s00401-015-1386-3","volume":"129","author":"KL Viola","year":"2015","unstructured":"Viola, K. L. & Klein, W. L. Amyloid \u03b2 oligomers in Alzheimer\u2019s disease pathogenesis, treatment, and diagnosis. Acta Neuropathol. 129, 183\u2013206 (2015).","journal-title":"Acta Neuropathol."},{"key":"73075_CR102","doi-asserted-by":"publisher","first-page":"5099","DOI":"10.1073\/pnas.0711731105","volume":"105","author":"W Hoyer","year":"2008","unstructured":"Hoyer, W., Gr\u00f6nwall, C., Jonsson, A., St\u00e5hl, S. & H\u00e4rd, T. Stabilization of a \u03b2-hairpin in monomeric Alzheimer\u2019s amyloid-\u03b2 peptide inhibits amyloid formation. Proc. Natl. Acad. Sci. USA. 105, 5099\u20135104 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"73075_CR103","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/aps.2011.14","volume":"32","author":"Q Nie","year":"2011","unstructured":"Nie, Q., Du, X. -g & Geng, M. -y Small molecule inhibitors of amyloid \u03b2 peptide aggregation as a potential therapeutic strategy for Alzheimer\u2019s disease. Acta Pharmacol. Sin. 32, 545\u2013551 (2011).","journal-title":"Acta Pharmacol. Sin."},{"key":"73075_CR104","doi-asserted-by":"publisher","first-page":"8458","DOI":"10.1038\/s41467-023-44307-7","volume":"14","author":"DJ Whiteside","year":"2023","unstructured":"Whiteside, D. J. et al. Synaptic density affects clinical severity via network dysfunction in syndromes associated with frontotemporal lobar degeneration. Nat. Commun. 14, 8458 (2023).","journal-title":"Nat. Commun."},{"key":"73075_CR105","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s42003-023-04961-5","volume":"6","author":"JM Krivinko","year":"2023","unstructured":"Krivinko, J. M. et al. Targeting the post-synaptic proteome has therapeutic potential for psychosis in Alzheimer Disease. Commun. Biol. 6, 598 (2023).","journal-title":"Commun. Biol."},{"key":"73075_CR106","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1038\/s42003-023-05511-9","volume":"6","author":"FC Ribeiro","year":"2023","unstructured":"Ribeiro, F. C. et al. Synaptic proteasome is inhibited in Alzheimer\u2019s disease models and associates with memory impairment in mice. Commun. Biol. 6, 1127 (2023).","journal-title":"Commun. Biol."},{"key":"73075_CR107","doi-asserted-by":"publisher","first-page":"381","DOI":"10.3233\/JAD-215280","volume":"85","author":"HM Wilkins","year":"2022","unstructured":"Wilkins, H. M. et al. Mitochondrial membrane potential influences amyloid-\u03b2 protein precursor localization and amyloid-\u03b2 secretion. J. Alzheimers Dis. 85, 381\u2013394 (2022).","journal-title":"J. Alzheimers Dis."},{"key":"73075_CR108","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/s41392-023-01547-9","volume":"8","author":"W Chen","year":"2023","unstructured":"Chen, W., Zhao, H. & Li, Y. Mitochondrial dynamics in health and disease: mechanisms and potential targets. Signal Trans. Target. Ther. 8, 333 (2023).","journal-title":"Signal Trans. Target. Ther."},{"key":"73075_CR109","doi-asserted-by":"publisher","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","volume":"26","author":"H Hampel","year":"2021","unstructured":"Hampel, H. et al. The amyloid-\u03b2 pathway in Alzheimer\u2019s disease. Mol. Psychiatry 26, 5481\u20135503 (2021).","journal-title":"Mol. Psychiatry"},{"key":"73075_CR110","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","volume":"8","author":"W Zhang","year":"2023","unstructured":"Zhang, W., Xiao, D., Mao, Q. & Xia, H. Role of neuroinflammation in neurodegeneration development. Signal Trans. Target. Ther. 8, 267 (2023).","journal-title":"Signal Trans. Target. Ther."},{"key":"73075_CR111","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1313-3","volume":"15","author":"EA Newcombe","year":"2018","unstructured":"Newcombe, E. A. et al. Inflammation: the link between comorbidities, genetics, and Alzheimer\u2019s disease. J. Neuroinflamm. 15, 276 (2018).","journal-title":"J. Neuroinflamm."},{"key":"73075_CR112","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","volume":"8","author":"C Gao","year":"2023","unstructured":"Gao, C., Jiang, J., Tan, Y. & Chen, S. Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Signal Trans. Target. Ther. 8, 359 (2023).","journal-title":"Signal Trans. Target. Ther."},{"key":"73075_CR113","first-page":"11","volume":"102","author":"N Beder","year":"2024","unstructured":"Beder, N., Belkhelfa, M. & Leklou, H. Involvement of inflammasomes in the pathogenesis of Alzheimer\u2019s disease. J. Alz. Dis. 102, 11\u201329 (2024).","journal-title":"J. Alz. Dis."},{"key":"73075_CR114","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57749","volume":"9","author":"AJ Granger","year":"2020","unstructured":"Granger, A. J. et al. Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner. eLife 9, e57749 (2020).","journal-title":"eLife"},{"key":"73075_CR115","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02367-6","volume":"8","author":"M Martineau","year":"2017","unstructured":"Martineau, M., Guzman, R. E., Fahlke, C. & Klingauf, J. VGLUT1 functions as a glutamate\/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses. Nat. Commun. 8, 2279 (2017).","journal-title":"Nat. Commun."},{"key":"73075_CR116","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52937-8","volume":"15","author":"A Hofmann","year":"2024","unstructured":"Hofmann, A. et al. Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer\u2019s disease. Nat. Commun. 15, 9982 (2024).","journal-title":"Nat. Commun."},{"key":"73075_CR117","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0333-5","volume":"14","author":"MA DeTure","year":"2019","unstructured":"DeTure, M. A. & Dickson, D. W. The neuropathological diagnosis of Alzheimer\u2019s disease. Mol. Neurodegener. 14, 32 (2019).","journal-title":"Mol. Neurodegener."},{"key":"73075_CR118","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1126\/science.6338589","volume":"219","author":"JT Coyle","year":"1983","unstructured":"Coyle, J. T., Price, D. L. & DeLong, M. R. Alzheimer\u2019s disease: a disorder of cortical cholinergic innervation. Science 219, 1184\u20131190 (1983).","journal-title":"Science"},{"key":"73075_CR119","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.nbd.2012.03.033","volume":"47","author":"EK Perry","year":"2012","unstructured":"Perry, E. K. et al. Neurogenic abnormalities in Alzheimer\u2019s disease differ between stages of neurogenesis and are partly related to cholinergic pathology. Neurobiol. Dis. 47, 155\u2013162 (2012).","journal-title":"Neurobiol. Dis."},{"key":"73075_CR120","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-024-00942-9","volume":"9","author":"X Feng","year":"2024","unstructured":"Feng, X. et al. A multi-targeting immunotherapy ameliorates multiple facets of Alzheimer\u2019s disease in 3xTg mice. npj Vaccines 9, 153 (2024).","journal-title":"npj Vaccines"},{"key":"73075_CR121","doi-asserted-by":"publisher","first-page":"101496","DOI":"10.1016\/j.arr.2021.101496","volume":"72","author":"D Jeremic","year":"2021","unstructured":"Jeremic, D., Jim\u00e9nez-D\u00edaz, L. & Navarro-L\u00f3pez, J. D. Past, present and future of therapeutic strategies against amyloid-\u03b2 peptides in Alzheimer\u2019s disease: a systematic review. Ageing Res. Rev. 72, 101496 (2021).","journal-title":"Ageing Res. Rev."},{"key":"73075_CR122","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1038\/s41593-024-01763-8","volume":"27","author":"J Gallego-Rudolf","year":"2024","unstructured":"Gallego-Rudolf, J. et al. Synergistic association of A\u03b2 and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults. Nat. Neurosci. 27, 2130\u20132137 (2024).","journal-title":"Nat. Neurosci."},{"key":"73075_CR123","doi-asserted-by":"publisher","first-page":"114366","DOI":"10.1016\/j.bcp.2020.114366","volume":"184","author":"J Yu","year":"2021","unstructured":"Yu, J. et al. Akt and calcium-permeable AMPA receptor are involved in the effect of pinoresinol on amyloid beta-induced synaptic plasticity and memory deficits. Biochem. Pharmacol. 184, 114366 (2021).","journal-title":"Biochem. Pharmacol."},{"key":"73075_CR124","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/B978-0-12-804766-8.00013-3","volume":"167","author":"JA Soria Lopez","year":"2019","unstructured":"Soria Lopez, J. A., Gonzalez, H. M. & Leger, G. C. Alzheimer\u2019s disease. Handb. Clin. Neurol. 167, 231\u2013255 (2019).","journal-title":"Handb. Clin. Neurol."},{"key":"73075_CR125","unstructured":"Case, D. A., et al. Amber 2023, (University of California, 2023)."},{"key":"73075_CR126","doi-asserted-by":"publisher","first-page":"6183","DOI":"10.1021\/acs.jcim.3c01153","volume":"63","author":"DA Case","year":"2023","unstructured":"Case, D. A. et al. AmberTools. J. Chem. Inf. Model. 63, 6183\u20136191 (2023).","journal-title":"J. Chem. Inf. Model."},{"key":"73075_CR127","doi-asserted-by":"publisher","first-page":"6161","DOI":"10.1073\/pnas.100121097","volume":"97","author":"SL Budd","year":"2000","unstructured":"Budd, S. L., Tenneti, L., Lishnak, T. & Lipton, S. A. Mitochondrial and extramitochondrial apoptotic signaling pathways in cerebrocortical neurons. Proc. Natl. Acad. Sci. USA 97, 6161\u20136166 (2000).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73075_CR128","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1038\/nm.1868","volume":"14","author":"H Du","year":"2008","unstructured":"Du, H. et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer\u2019s disease. Nat. Med. 14, 1097\u20131105 (2008).","journal-title":"Nat. Med."},{"key":"73075_CR129","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1038\/nprot.2006.116","volume":"1","author":"CV Vorhees","year":"2006","unstructured":"Vorhees, C. V. & Williams, M. T. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat. Protoc. 1, 848\u2013858 (2006).","journal-title":"Nat. Protoc."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73075-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73075-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73075-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:02:11Z","timestamp":1784228531000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73075-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":129,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["73075"],"URL":"https:\/\/doi.org\/10.1038\/s41467-026-73075-3","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]},"assertion":[{"value":"19 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare the competing interests. A patent application for this work is filed under Jianfeng Cai, Heng Liu, Donghui Zhu and Firoz Akhter. The remaining authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"6324"}}