{"id":126763,"date":"2024-11-17T04:43:45","date_gmt":"2024-11-16T21:43:45","guid":{"rendered":"https:\/\/hotvideos24.online\/?p=126763"},"modified":"2024-11-17T04:43:45","modified_gmt":"2024-11-16T21:43:45","slug":"alzheimers-linked-to-key-proteins-via-cerebrospinal-fluid-analysis","status":"publish","type":"post","link":"https:\/\/hotvideos24.online\/?p=126763","title":{"rendered":"Alzheimer\u2019s Linked to Key Proteins via Cerebrospinal Fluid Analysis"},"content":{"rendered":"<p> <script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js?client=ca-pub-3711241968723425\"\r\n     crossorigin=\"anonymous\"><\/script>\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-format=\"fluid\"\r\n     data-ad-layout-key=\"-fb+5w+4e-db+86\"\r\n     data-ad-client=\"ca-pub-3711241968723425\"\r\n     data-ad-slot=\"7910942971\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script><br \/>\n<\/p>\n<div>\n<p><strong>Summary: <\/strong>Using cerebrospinal fluid from living patients, researchers have identified specific proteins and genetic pathways involved in the development and progression of Alzheimer\u2019s disease. This proteomic analysis revealed 38 proteins likely to play causal roles in Alzheimer\u2019s, 15 of which are potential drug targets.<\/p>\n<p>The study provides a clearer understanding of how genetic and protein interactions drive neurodegeneration, offering new avenues for therapeutic development. These findings highlight the power of human-derived samples for studying brain disorders and may also benefit research into other neurological conditions.<\/p>\n<p><strong>Key Facts<\/strong>:<\/p>\n<ul class=\"wp-block-list\">\n<li>Cerebrospinal fluid analysis identified 38 proteins linked to Alzheimer\u2019s progression.<\/li>\n<li>Of these proteins, 15 are potential targets for future drug therapies.<\/li>\n<li>The study demonstrates the importance of human-derived data in understanding neurodegeneration.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>WUSTL<\/p>\n<p><strong>A multitude of genes have been linked to the development of Alzheimer\u2019s disease. Specifically how those genes might influence the progression of neurodegeneration remains something of a black box though, in part because of the challenges of examining in molecular detail the brain of a living patient.<\/strong><\/p>\n<p>Using cerebrospinal fluid (CSF) collected from living patients, a team of researchers at Washington University School of Medicine in St. Louis has for the first time linked disease-related proteins and genes to identify specific cellular pathways responsible for Alzheimer\u2019s genesis and progression. Because these proteins were gathered from CSF, they are a good proxy for activity in the brain, and several of them may be potential targets for therapies.<\/p>\n<figure class=\"wp-block-image size-full\"><picture fetchpriority=\"high\" decoding=\"async\" class=\"wp-image-106248\"><source type=\"image\/webp\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience.jpg.webp 1200w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-300x200.jpg.webp 300w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-770x513.jpg.webp 770w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-1155x770.jpg.webp 1155w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-370x247.jpg.webp 370w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-293x195.jpg.webp 293w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-150x100.jpg.webp 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/><img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"800\" src=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience.jpg\" alt=\"This shows a brain.\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience.jpg 1200w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-300x200.jpg 300w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-770x513.jpg 770w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-1155x770.jpg 1155w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-370x247.jpg 370w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-293x195.jpg 293w, https:\/\/neurosciencenews.com\/files\/2024\/11\/alzheimers-genetic-cerebrospinal-fluid-neuroscience-150x100.jpg 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/> <\/picture><figcaption class=\"wp-element-caption\">However, knowing the gene or region of DNA associated with the disease is only the first step. Credit: Neuroscience News<\/figcaption><\/figure>\n<p>The findings are available in<em>\u00a0Nature Genetics.<\/em><\/p>\n<p>The use of patients\u2019 CSF is a step forward for such studies and may be the best way to acquire relevant samples that help map out the constellation of protein activity, known as the proteome, said\u00a0Carlos Cruchaga, PhD, the Barbara Burton and Reuben Morriss III professor of psychiatry and director of the\u00a0NeuroGenomics and Informatics Center at WashU Medicine.<\/p>\n<p>\u201cOur goal is to identify risk-linked and protective genes, and also identify the causal role they play,\u201d Cruchaga said.<\/p>\n<p>\u201cTo do that, we need to study human-derived data. That is why we decided to do a large proteomic study of cerebrospinal fluid, because we know that CSF is a good representation of the pathology of the disease.\u201d<\/p>\n<p>Cruchaga explained that similar investigations have relied on brain tissues collected postmortem, and therefore only provide information about the later stages of Alzheimer\u2019s. Other studies have looked at blood plasma, which is not specific to the tissues affected by the disease.<\/p>\n<p>In the past decade and a half of researching Alzheimer\u2019s disease, scientists have increased the number of regions of our genome known to be associated with the condition from 10 to nearly 80. However, knowing the gene or region of DNA associated with the disease is only the first step.<\/p>\n<p>Linking an individual\u2019s proteomic profile \u2013 that is, which proteins are active and to what degree \u2013 to their genetic code establishes a holistic view of the cellular activities in the brain. By comparing CSF samples from people with and without Alzheimer\u2019s disease, the researchers could then identify which cellular pathways are dysfunctional.<\/p>\n<p>\u201cSometimes within a region of DNA known to be associated with Alzheimer\u2019s there are many genes, and we don\u2019t know which of those genes are driving the medical condition,\u201d Cruchaga said.<\/p>\n<p>\u201cBy adding the proteins to the analysis, we can determine the gene driving the association, determine the molecular pathway that they are part of, as well as to identify novel protein-to-protein interactions that otherwise will not be possible.\u201d<\/p>\n<p>Cruchaga and his collaborators had access to a rich database of information through the Knight-ADRC and the Dominantly Inherited Alzheimer Network (DIAN), which are based at WashU Medicine, as well as other studies through their collaborators.<\/p>\n<p>These studies were also able to provide the genetic information and CSF samples of 3,506 individuals, both healthy donors and those with Alzheimer\u2019s disease.<\/p>\n<p>The team cross-referenced proteomic data from the CSF samples with existing studies that had identified areas of the genome correlated with Alzheimer\u2019s. From this process, they narrowed in on 1,883 proteins of the 6,361 in the CSF proteomic atlas.<\/p>\n<p>The investigators used three different established statistical analyses that can identify with high confidence genes and proteins that are part of the biological pathways leading to the disease.<\/p>\n<p>With this technique, they determined that 38 proteins are likely to have causal effects in Alzheimer\u2019s progression; 15 of these can be targeted by medicines.<\/p>\n<p>\u201cThe novelty and the strength of this analysis is that we have defined proteins that modify risk,\u201d Cruchaga said. \u201cSo now that we have the causal steps, we can establish where the steps are leading to in the brain.\u201d<\/p>\n<p>The immediate implications for understanding and developing treatments for Alzheimer\u2019s from this study are significant, but Cruchaga said he believes that CSF proteomics may yield a treasure trove of information for many neurological conditions, ranging from Parkinson\u2019s disease to schizophrenia.<\/p>\n<p>\u201cThat\u2019s the power of this approach \u2013 once you have an atlas of genetic variants, and that of the protein levels, you can apply this to any disease,\u201d he said.<\/p>\n<p>Proteins are not the only key to unlocking these conditions to be found in the CSF. Cruchaga also is investigating the potential of metabolites \u2013 substances released by cells when breaking down other compounds as part of their routine processes that are also found in CSF.<\/p>\n<p>In a separate paper, also published in <em>Nature Genetics<\/em>, he and his collaborators demonstrated the promise of this approach and reported associations between specific metabolites and conditions including Parkinson\u2019s disease, diabetes and dementia.<\/p>\n<p>Western D, Timsina J, Wang L, Wang C, Yang C, Phillips B, Wang Y, Liu M, Ali M, Beric A, Gorijala P, Kohlfeld P, Budde J, Levey AI, Morris JC, Perrin RJ, Ruiz A, Marqui\u00e9 M, Boada M, de Rojas I, Rutledge J, Oh H, Wilson EN, Le Guen Y, Reus LM, Tijms B, Jelle Visser P, van der Lee SJ, Pijnenburg YAL, Teunissen CE, del Campo Milan M,\u00a0 Alvarez I, Aguilar M, Dominantly Inherited Alzheimer Network (DIAN), the Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI), Greicius MD, Pastor P, Pulford DJ, Ibanez l, Wyss-Coray T, Sung YJ, Cruchaga C.<\/p>\n<p>Cruchaga has received research support from GSK and Eisai. The funders of the study had no role in the collection, analysis or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Cruchaga is a member of the advisory board of Circular Genomics and owns stocks in this company.<\/p>\n<p><strong>Funding: <\/strong>This work was supported by grants from the National Institutes of Health (NIH), R01AG044546, P01AG00399, RF1AG053303, RF1AG058501, U01AG058922, RF1AG074007, R00AG062723, P30 AG066515, NIH P30AG066444, P01AG03991, P01AG026276 the Chan Zuckerberg Initiative, the Michael J. Fox Foundation, the Department of Defense W81XWH2010849, the Alzheimer\u2019s Association Zenith Fellows Award ZEN-22-848604, Bright Focus Foundation A2021033S.<\/p>\n<p>Alzheimer Nederland WE.03-2018-05, Selfridges Group Foundation NR170065. GlaxoSmithKline (GSK) provided funding to support the analyses performed in this study.<\/p>\n<p>The Dominantly Inherited Alzheimer\u2019s Network is supported by U19AG032438, SG-20-690363-DIAN, ADNI U01 AG024904 Department of Defense W81XWH-12-2-0012). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.<\/p>\n<p>Wang C, Yang C, Western D, Ali M, Wang Y, Phuah C-L, Budde J, Wang L, Gorijala P, Timsina J, \u00a0Ruiz A, Pastor P, Fernandez MV, Dominantly Inherited Alzheimer Network (DIAN), The Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI), Panyard DJ, Engelman CD, Deming Y, Boada M, Cano A, Garcia-Gonzalez P, Neill R, Graff-Radford NR, Mori H, Lee J-H, Perrin RJ, Ibanez L, Sung YJ, \u00a0Cruchaga C.<\/p>\n<p>Cruchaga has received research support from GSK and EISAI and is a member of the advisory board of Circular Genomics and owns stocks.<\/p>\n<p><strong>Funding: <\/strong>This work was supported by grants from the National Institutes of Health (NIH; R01AG044546,P01AG003991, RF1AG053303, RF1AG058501, U01AG058922, RF1AG074007, R01\/ RF1AG054047, the Chan Zuckerberg Initiative, the Michael J. Fox Foundation, the Department of Defense LI-W81XWH2010849, the Alzheimer\u2019s Association Zenith Fellows Award ZEN-22-848604, and an anonymous foundation.<\/p>\n<p>Recruitment and clinical characterization of research participants at were supported by NIH P30AG066444, P01AG03991, P01AG026276.<\/p>\n<p>Data collection and sharing was supported by the DIAN U19AG032438 and funded by the National Institute on Aging (NIA), the Alzheimer\u2019s Association SG-20-690363-DIAN, ADNI NIH grant U01 AG024904and DOD ADNI W81XWH-12-2-0012. \u00a0<\/p>\n<p>Further support came from the Spanish Ministry of Science, Innovation and Universities FJC2018-036012-I, Instituto de Salud Carlos III (ISCIII) CD22\/00125, Proyectos de Generaci\u00f3n de Conocimiento PID2021-122473OA-I00.<\/p>\n<p>The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.<\/p>\n<h2 class=\"wp-block-heading\">About this Alzheimer\u2019s disease and genetics research news<\/h2>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"http:\/\/neurosciencenews.com\/cdn-cgi\/l\/email-protection#14663a7975667f5463616760783a717061\" target=\"_blank\" rel=\"noreferrer noopener\">Mark Reynolds<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/wustl.edu\" target=\"_blank\" rel=\"noreferrer noopener\">WUSTL<\/a><br \/><strong>Contact: <\/strong>Mark Reynolds \u2013 WUSTL<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>Closed access.<br \/>\u201c<a href=\"https:\/\/www.nature.com\/articles\/s41588-024-01972-8\" target=\"_blank\" rel=\"noreferrer noopener\">Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer\u2019s disease<\/a>\u201d by Carlos Cruchaga et al. <em>Nature Genetics<\/em><\/p>\n<hr class=\"wp-block-separator has-text-color has-pale-cyan-blue-color has-alpha-channel-opacity has-pale-cyan-blue-background-color has-background\"\/>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer\u2019s disease<\/strong><\/p>\n<p>The integration of quantitative trait loci (QTLs) with disease genome-wide association studies (GWASs) has proven successful in prioritizing candidate genes at disease-associated loci. QTL mapping has been focused on multi-tissue expression QTLs or plasma protein QTLs (pQTLs).<\/p>\n<p>We generated a cerebrospinal fluid (CSF) pQTL atlas by measuring 6,361 proteins in 3,506 samples. We identified 3,885 associations for 1,883 proteins, including 2,885 new pQTLs, demonstrating unique genetic regulation in CSF.<\/p>\n<p>We identified CSF-enriched pleiotropic regions on chromosome (chr)3q28 near\u00a0<em>OSTN<\/em>\u00a0and chr19q13.32 near\u00a0<em>APOE<\/em>\u00a0that were enriched for neuron specificity and neurological development.<\/p>\n<p>We integrated our associations with Alzheimer\u2019s disease (AD) through proteome-wide association study (PWAS), colocalization and Mendelian randomization and identified 38 putative causal proteins, 15 of which have drugs available.<\/p>\n<p>Finally, we developed a proteomics-based AD prediction model that outperforms genetics-based models.<\/p>\n<p>These findings will be instrumental to further understand the biology and identify causal and druggable proteins for brain and neurological traits.<\/p>\n<p> <!-- Form created by Optin Forms plugin by WPKube: create beautiful optin forms with ease! --> <!-- https:\/\/wpkube.com\/ --><!--optinforms-form5-container--> <!-- \/ Optin Forms --> <\/div>\n<p><script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js?client=ca-pub-3711241968723425\"\r\n     crossorigin=\"anonymous\"><\/script>\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-format=\"fluid\"\r\n     data-ad-layout-key=\"-fb+5w+4e-db+86\"\r\n     data-ad-client=\"ca-pub-3711241968723425\"\r\n     data-ad-slot=\"7910942971\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script><br \/>\n<br \/><div data-type=\"_mgwidget\" data-widget-id=\"1660802\">\r\n<\/div>\r\n<script>(function(w,q){w[q]=w[q]||[];w[q].push([\"_mgc.load\"])})(window,\"_mgq\");\r\n<\/script>\r\n<br \/>\n<br \/><a href=\"https:\/\/neurosciencenews.com\/alzheimers-csf-genetics-28067\/\">Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Summary: Using cerebrospinal fluid from living patients, researchers have identified specific proteins and genetic pathways involved in the development and progression of Alzheimer\u2019s disease. This proteomic analysis revealed 38 proteins &hellip; <a href=\"https:\/\/hotvideos24.online\/?p=126763\" class=\"more-link\">Read More<\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[],"class_list":["post-126763","post","type-post","status-publish","format-standard","hentry","category-health","entry"],"_links":{"self":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/posts\/126763","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=126763"}],"version-history":[{"count":0,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=\/wp\/v2\/posts\/126763\/revisions"}],"wp:attachment":[{"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=126763"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=126763"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/hotvideos24.online\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=126763"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}