{"id":217697,"date":"2025-07-12T06:03:31","date_gmt":"2025-07-12T11:03:31","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2025\/07\/abstract-synaptic-plasticity-is-obstructed-by-pathogenic-tau-in-the-brain"},"modified":"2025-07-12T06:03:31","modified_gmt":"2025-07-12T11:03:31","slug":"abstract-synaptic-plasticity-is-obstructed-by-pathogenic-tau-in-the-brain","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2025\/07\/abstract-synaptic-plasticity-is-obstructed-by-pathogenic-tau-in-the-brain","title":{"rendered":"Abstract: Synaptic plasticity is obstructed by pathogenic tau in the brain"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/abstract22.jpg\"><\/a><\/p>\n<p>Representing a key mechanism that underlies memory loss in Alzheimer\u2019s disease (AD) and related tauopathies. Here, we found that reduced levels of the memory-associated protein KIdney\/BRAin (KIBRA) in the brain and increased KIBRA protein levels in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. We next defined a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIBRA protein (CT-KIBRA). We showed that CT-KIBRA restored plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we found that CT-KIBRA stabilized the protein kinase M\u03b6 (PKM\u03b6) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. Thus, our results distinguished KIBRA both as a biomarker of synapse dysfunction and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy.<\/p>\n<hr>\n<p>\n<sup>1<\/sup>Buck Institute for Research on Aging, Novato, California, USA.<\/p>\n<p><sup>2<\/sup>Memory and Aging Center, Department of <i>Neurology<\/i>, University of California San Francisco, San Francisco, California, USA.<\/p>\n<p><sup>3<\/sup>Gladstone Institutes, San Francisco, Califoria, USA.<\/p>\n<p><sup>4<\/sup>Weill Institute for Neurosciences, Department of Pathology, University of California San Francisco, San Francisco, California, USA.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Representing a key mechanism that underlies memory loss in Alzheimer\u2019s disease (AD) and related tauopathies. Here, we found that reduced levels of the memory-associated protein KIdney\/BRAin (KIBRA) in the brain and increased KIBRA protein levels in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. We next defined a mechanism for [\u2026]<\/p>\n","protected":false},"author":534,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,269,47],"tags":[],"class_list":["post-217697","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-life-extension","category-neuroscience"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/217697","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/534"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=217697"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/217697\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=217697"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=217697"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=217697"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}