{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:06:22Z","timestamp":1785827182656,"version":"3.56.0"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"13","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Fondazione Sacchetti","award":["2023-2025"],"award-info":[{"award-number":["2023-2025"]}]},{"name":"Mario Negri Alumni Association","award":["2025"],"award-info":[{"award-number":["2025"]}]},{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2024-NAZ-0018"],"award-info":[{"award-number":["2024-NAZ-0018"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondazione Caripo\/Telethon","award":["Telethon GJC23044"],"award-info":[{"award-number":["Telethon GJC23044"]}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["IG 2024 ID 30307"],"award-info":[{"award-number":["IG 2024 ID 30307"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universit\u00e0 di Milano Seed 4 Innovation","award":["2024"],"award-info":[{"award-number":["2024"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,31]]},"abstract":"<jats:p>\n                    Interactions between amyloidogenic proteins are emerging as critical drivers of neurodegenerative diseases. Among others, in Alzheimer\u2019s disease (AD) and severe forms of chronic traumatic encephalopathy (CTE), codeposition of tau and amyloid-\u03b2 (A\u03b2) leads to worsening of clinical outcomes and disease progression. Despite the importance of such heterotypic interactions, the underlying molecular mechanisms have proven challenging to be established. Here, we investigated the direct interaction between A\u03b2 and tau, combining in vitro reconstruction, and in vivo models. We find that characteristic AD paired helical filament (PHF) and CTE folds catalyze the primary nucleation of A\u03b242 in a fold-specific manner with enzyme-like kinetics. In particular, CTE fibrils exhibit the highest catalytic activity and constrain A\u03b242 polymorphism, suggesting templating effects. Moreover, PHF and CTE tau fibrils increase A\u03b242 toxicity in SH-SY5Y neuroblastoma cells and transgenic\n                    <jats:italic toggle=\"yes\">Caenorhabditis elegans,<\/jats:italic>\n                    preserving fold-dependent reactivities. Our findings shed light on the molecular mechanisms of heterotypic interaction between amyloidogenic proteins in disease-relevant conditions, highlighting the role of amyloid structure and recognition mechanisms as key determinants. These results offer insights into the pathological mechanisms of multiple proteinopathies. The mechanisms described here might be used as a blueprint for structure-based design of new therapeutic agents targeting specific amyloidogenic interactions.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2532775123","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:07:16Z","timestamp":1774462036000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Tau catalyzes amyloid-\u03b2 aggregation and toxicity in a polymorph-dependent manner"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4409-8516","authenticated-orcid":false,"given":"Michele","family":"Mosconi","sequence":"first","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri Scientific Institutes for Research, Hospitalization and Healthcare","place":["Milano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8691-0826","authenticated-orcid":false,"given":"Chiara","family":"Leonardi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri Scientific Institutes for Research, Hospitalization and Healthcare","place":["Milano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zev","family":"Armour-Garb","sequence":"additional","affiliation":[{"name":"Center for Misfolding Diseases, Yusuf Hamied Department of Chemistry, Cambridge University","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Rocutto","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri Scientific Institutes for Research, Hospitalization and Healthcare","place":["Milano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-6704","authenticated-orcid":false,"given":"Marten","family":"Beeg","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri Scientific Institutes for Research, Hospitalization and Healthcare","place":["Milano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6562-7715","authenticated-orcid":false,"given":"Georg","family":"Meisl","sequence":"additional","affiliation":[{"name":"Center for Misfolding Diseases, Yusuf Hamied Department of Chemistry, Cambridge University","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0656-9225","authenticated-orcid":false,"given":"Lei","family":"Ortigosa-Pascual","sequence":"additional","affiliation":[{"name":"Biochemistry and Structural Biology, Department of Chemistry, Lund University","place":["Lund, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9472-6854","authenticated-orcid":false,"given":"Luca","family":"Broggini","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Universit\u00e0 degli Studi di Milano","place":["Milano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-9873","authenticated-orcid":false,"given":"Mario","family":"Salmona","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri Scientific Institutes for Research, Hospitalization and Healthcare","place":["Milano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6678-5873","authenticated-orcid":false,"given":"Stefano","family":"Ricagno","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Universit\u00e0 degli Studi di Milano","place":["Milano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7879-0140","authenticated-orcid":false,"given":"Tuomas P. J.","family":"Knowles","sequence":"additional","affiliation":[{"name":"Center for Misfolding Diseases, Yusuf Hamied Department of Chemistry, Cambridge University","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2258-0531","authenticated-orcid":false,"given":"Luisa","family":"Diomede","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri Scientific Institutes for Research, Hospitalization and Healthcare","place":["Milano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0235-9"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlac065"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-024-00461-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.022"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218402110"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00454"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50692-4"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2220075121"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-69377-1"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03911-7"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05319-3"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2317-6"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03164-5"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-025-01498-5"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23002"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1026-5"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.31083\/j.fbl2810255"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12485"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12424"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.09.048"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4SC02517B"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpclett.4c02827"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201105877"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c03212"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06788-w"},{"key":"e_1_3_4_27_2","article-title":"Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments","volume":"14","author":"L\u00f6vestam S.","year":"2025","unstructured":"S. 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