{"id":218848,"date":"2025-09-11T18:40:10","date_gmt":"2025-09-11T18:40:10","guid":{"rendered":"https:\/\/www.europesays.com\/us\/218848\/"},"modified":"2025-09-11T18:40:10","modified_gmt":"2025-09-11T18:40:10","slug":"defective-exosome-production-linked-to-alzheimers-gene-mutation","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/218848\/","title":{"rendered":"Defective Exosome Production Linked to Alzheimer\u2019s Gene Mutation"},"content":{"rendered":"<p><strong>Summary: <\/strong>New research reveals that a gene mutation tied to Alzheimer\u2019s disease disrupts the production of exosomes, tiny cellular particles essential for communication between brain cells. Cells with a defective SORLA protein produced about 30% fewer exosomes, and those exosomes were up to 50% less effective at supporting cell growth.<\/p>\n<p>This weakened communication could accelerate the development of Alzheimer\u2019s by reducing the brain\u2019s ability to maintain healthy tissue. The findings suggest new therapeutic strategies that could focus on restoring exosome production or improving their quality.<\/p>\n<p><strong>Key Facts<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li><strong>SORLA Mutation:<\/strong> Linked to 30% fewer exosomes and weaker brain cell support.<\/li>\n<li><strong>Communication Breakdown:<\/strong> Defective exosomes were up to 50% less effective at stimulating neighboring cells.<\/li>\n<li><strong>Treatment Potential:<\/strong> Boosting exosome function could open new Alzheimer\u2019s therapies.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>Aarhus University<\/p>\n<p><strong>They\u2019re tiny particles \u2013 with potentially huge human consequences. <\/strong><\/p>\n<p>Researchers from Aarhus University have identified a defect in the production of so-called exosomes in cells, associated with a mutation seen in dementia patients. This could lead to a better understanding of the development \u2013 and perhaps even a treatment \u2013 of Alzheimer\u2019s.<\/p>\n<p>  <img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"800\" src=\"https:\/\/www.europesays.com\/us\/wp-content\/uploads\/2025\/09\/alzheimrs-exosome-neuroscience.jpg\" alt=\"This shows neurons and DNA.\"  \/> What Kristian Juul-Madsen and his research colleagues have now discovered is that if the SORLA-protein is defective, the brain cells become significantly worse at producing exosomes. Credit: Neuroscience News<\/p>\n<p>Exosomes are the epitome of microscopic. So small that just the tip of a grain of rice equals millions of them. Nevertheless, new research from the Department of Biomedicine at Aarhus University shows that they may play a key role in the development of Alzheimer\u2019s.<\/p>\n<p>Assistant Professor Kristian Juul-Madsen is one of the researchers behind a new study recently published in the scientific journal\u00a0Alzheimer\u2019s &amp; Dementia: The Journal of the Alzheimer\u2019s Association.<\/p>\n<p>\u201cExosomes are used to communicate with and activate surrounding cells, and we have now identified a defect in both the production and the quality of exosomes in cells that we know are predisposed to Alzheimer\u2019s.\u201d<\/p>\n<p>To date, four main genes have been identified that can be linked to the inherited form Alzheimer\u2019s. And to understand the new research findings, we need to dive a bit into the technical explanations. One of these four genes is called\u00a0Sorl1. This gene encodes the protein\u00a0SORLA. And when the SORLA-protein mutates, there is a risk of developing Alzheimer\u2019s.<\/p>\n<p>What Kristian Juul-Madsen and his research colleagues have now discovered is that if the SORLA-protein is defective, the brain cells become significantly worse at producing exosomes.<\/p>\n<p>\u201cWe found that cells with this mutation produced 30% fewer exosomes, and those that were produced were significantly worse at stimulating the growth and maturation of surrounding cells \u2013 in fact, up to 50% less effective than in cells where the SORLA-protein is not mutated.\u201d<\/p>\n<p>And this could be crucial for future Alzheimer\u2019s research, he says.<\/p>\n<p>\u201cIt tells us that exosomes produced particularly by the brain\u2019s immune cells play an important role in maintaining brain health \u2013 and that mutations leading to fewer and poorer quality exosomes are associated with increased risk of Alzheimer\u2019s.\u201d<\/p>\n<p>Kristian Juul-Madsen hopes that the research findings may eventually lead to improved treatment of Alzheimer\u2019s.<\/p>\n<p>\u201cThe potential is very clear. We now have the opportunity to investigate new treatments for Alzheimer\u2019s \u2013 either by stimulating the function of SORLA so that the cells produce more and better exosomes, or by targeting other known receptors that can enhance exosome production.\u201d<\/p>\n<p>Alzheimer\u2019s is the most common form of age-related dementia in Denmark. It is estimated that around 55,000 Danes are affected, and there is currently no treatment for the disease.<\/p>\n<p>Behind the research \u2013 more information\u00a0<\/p>\n<ul class=\"wp-block-list\">\n<li><strong>Study type<\/strong>: Basic research, primarily based on the use of iPSCs (induced pluripotent stem cells). We generate new stem cells that contain the mutation we want to study and compare them to cells without this disease-associated mutation. In addition, the study relies on extensive \u201comics\u201d analyses, where we examined globally both the protein and RNA content of exosomes.<\/li>\n<li><strong>Collaborators<\/strong>: The study was carried out as an LF Postdoc project. I therefore worked in Thomas Willnow\u2019s laboratory at the Max Delbr\u00fcck Center for Molecular Medicine in Berlin and in his laboratory at the Department of Biomedicine at Aarhus University.<\/li>\n<li><strong>External funding<\/strong>: The study was primarily supported by an LF postdoctoral grant from the Lundbeck Foundation (R380-2021-1326) awarded to Kristian Juul-Madsen, and by a Laureate grant from the Novo Nordisk Foundation (NNF18OC0033928) and a research grant from the Alzheimer Forschung Initiative (18003) awarded to Prof. Thomas Willnow.<\/li>\n<li><strong>Potential conflicts of interest<\/strong>: None.<\/li>\n<\/ul>\n<p>About this Alzheimer\u2019s disease research news<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"http:\/\/neurosciencenews.com\/cdn-cgi\/l\/email-protection#bdcbd4dfd8d3fddcc893d9d6\" target=\"_blank\" rel=\"noreferrer noopener nofollow\">Vibe Noordeloos<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/au.dk\" target=\"_blank\" rel=\"noreferrer noopener nofollow\">Aarhus University<\/a><br \/><strong>Contact: <\/strong>Vibe Noordeloos \u2013 Aarhus University<br \/><strong>Image: <\/strong>The image is credited to Neuroscience News<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Original Research: <\/strong>Open access.<br \/>\u201c<a href=\"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full\/10.1002\/alz.70591\" target=\"_blank\" rel=\"noreferrer noopener nofollow\">Familial Alzheimer\u2019s disease mutation identifies novel role of SORLA in release of neurotrophic exosomes<\/a>\u201d by Kristian Juul-Madsen et al. Alzheimer\u2019s &amp; Dementia<\/p>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>Familial Alzheimer\u2019s disease mutation identifies novel role of SORLA in release of neurotrophic exosomes<\/strong><\/p>\n<p>INTRODUCTION<\/p>\n<p>Mutations in\u00a0SORL1, encoding the sorting receptor Sortilin-related receptor with A-type repeats (SORLA), are found in individuals with Alzheimer\u2019s disease (AD). We studied SORLAN1358S, carrying a mutation in its ligand binding domain, to learn more about receptor functions relevant for human brain health.<\/p>\n<p>METHODS<\/p>\n<p>We investigated consequences of SORLAN1358S\u00a0expression in induced pluripotent stem cell (iPSC)-derived human neurons and microglia, using unbiased proteome screens and functional cell assays.<\/p>\n<p>RESULTS<\/p>\n<p>We identified alterations in the SORLAN1358S\u00a0interactome linked to biogenesis of exosomes. Consequently, the mutant receptor failed to promote release and neurotrophic qualities of exosomes, a defect attributed to altered exosomal content of microRNAs controlling neuronal maturation.<\/p>\n<p>DISCUSSION<\/p>\n<p>We identified a role for SORLA in controlling quantity and neurotrophic quality of exosomes secreted by cells, suggesting impaired cellular cross talk through exosomes as a pathological trait contributing to AD pathology in carriers of\u00a0SORL1\u00a0variants.<\/p>\n<p>Highlights<\/p>\n<ul class=\"wp-block-list\">\n<li>Familial Alzheimer\u2019s disease mutation in\u00a0SORL1\u00a0changes interactome of mutant Sortilin-related receptor with A-type repeats (SORLA).<\/li>\n<li>Mutant SORLA impairs release of exosomes from neurons and microglia.<\/li>\n<li>Mutant exosomes lack neurotrophic qualities.<\/li>\n<li>Defect linked to alterations in microRNA content.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"Summary: New research reveals that a gene mutation tied to Alzheimer\u2019s disease disrupts the production of exosomes, tiny&hellip;\n","protected":false},"author":3,"featured_media":218849,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[55873,10263,827,116706,815,829,912,831,159,67,132,68],"class_list":{"0":"post-218848","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-aarhus-university","9":"tag-alzheimers-disease","10":"tag-brain-research","11":"tag-exosomes","12":"tag-genetics","13":"tag-neurobiology","14":"tag-neurology","15":"tag-neuroscience","16":"tag-science","17":"tag-united-states","18":"tag-unitedstates","19":"tag-us"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/115187130305695220","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/218848","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=218848"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/218848\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/218849"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=218848"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=218848"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=218848"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}