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Trans. R. Soc. B"],"published-print":{"date-parts":[[2024,7,29]]},"abstract":"<jats:p>How the two pathognomonic proteins of Alzheimer\u2019s disease (AD); amyloid \u00df (A\u00df) and tau, cause synaptic failure remains enigmatic. Certain synthetic and recombinant forms of these proteins are known to act concurrently to acutely inhibit long-term potentiation (LTP). Here, we examined the effect of early amyloidosis on the acute disruptive action of synaptotoxic tau prepared from recombinant protein and tau in patient-derived aqueous brain extracts. We also explored the persistence of the inhibition of LTP by different synaptotoxic tau preparations. A single intracerebral injection of aggregates of recombinant human tau that had been prepared by either sonication of fibrils (S\u03c4As) or disulfide bond formation (oTau) rapidly and persistently inhibited LTP in rat hippocampus. The threshold for the acute inhibitory effect of oTau was lowered in amyloid precursor protein (APP)-transgenic rats. A single injection of synaptotoxic tau-containing AD or Pick\u2019s disease brain extracts also inhibited LTP, for over two weeks. Remarkably, the persistent disruption of synaptic plasticity by patient-derived brain tau was rapidly reversed by a single intracerebral injection of different anti-tau monoclonal antibodies, including one directed to a specific human tau amino acid sequence. We conclude that patient-derived LTP-disrupting tau species persist in the brain for weeks, maintaining their neuroactivity often in concert with A\u00df.<\/jats:p>\n                  <jats:p>This article is part of a discussion meeting issue \u2018Long-term potentiation: 50 years on\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2023.0234","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T03:05:53Z","timestamp":1717988753000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Rapidly reversible persistent long-term potentiation inhibition by patient-derived brain tau and amyloid \u00df proteins"],"prefix":"10.1098","volume":"379","author":[{"given":"Tomas","family":"Ondrejcak","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Medicine, and Institute of Neuroscience, Trinity College , Dublin 2, Republic of Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Klyubin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Medicine, and Institute of Neuroscience, Trinity College , Dublin 2, Republic of Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neng-Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Medicine, and Institute of Neuroscience, Trinity College , Dublin 2, Republic of Ireland"},{"name":"Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue , Zhengzhou 450001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Medicine, and Institute of Neuroscience, Trinity College , Dublin 2, Republic of Ireland"},{"name":"Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue , Zhengzhou 450001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiancheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Physics and Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Dublin 4, Republic of Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"School of Physics and Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Dublin 4, Republic of Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3867-9536","authenticated-orcid":true,"given":"Michael J.","family":"Rowan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Medicine, and Institute of Neuroscience, Trinity College , Dublin 2, Republic of Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcac083"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00749-z"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-042921-023749"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0687-6"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.02.015"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.029"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep19393"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0166-19.2019"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1700-18.2018"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01589-5"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.04.007"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0082-23.2023"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01309-6"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.04.020"},{"key":"e_1_3_8_18_2","first-page":"101","article-title":"Mechanisms of cell-to-cell transmission of pathological Tau: a review","volume":"76","author":"Gibbons GS","year":"2019","unstructured":"Gibbons GS , Lee VMY , Trojanowski JQ . 2019 Mechanisms of cell-to-cell transmission of pathological Tau: a review. 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