Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model
Cerebrospinal fluid (CSF) has been implicated in amyotrophic lateral sclerosis (ALS) due to its ability to spread inflammatory proteins throughout the nervous system. We hypothesized that filtration of the CSF could remove pathogenic proteins and prevent them from altering motor phenotypes in a mous...
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creator | Venkatraman, Vishal Filiano, Anthony J Xu, Li Collins, Leonard Luo, Emily Ripple, Katelyn M de Castro, George C Boua, Jane-Valeriane K Marius, Choiselle Giamberardino, Charles Lad, Shivanand P Islam Williams, Taufika Bereman, Michael S Bedlack, Richard S |
description | Cerebrospinal fluid (CSF) has been implicated in amyotrophic lateral sclerosis (ALS) due to its ability to spread inflammatory proteins throughout the nervous system. We hypothesized that filtration of the CSF could remove pathogenic proteins and prevent them from altering motor phenotypes in a mouse model.
We filtered the CSF from 11 ALS patients via 100 kilodaltons (kD) molecular weight cut-off filters. We used mass spectrometry-based discovery proteomics workflows to compare protein abundances before and after filtration. To test the effects of CSF filtration on motor function, we injected groups of mice with saline, filtered ALS-CSF, or unfiltered ALS-CSF (n=12 per group) and assessed motor function via pole descent and open field tests.
We identified proteins implicated in ALS pathogenesis and showed that these were removed in significant amounts in our workflow. Key filtered proteins included complement proteins, chitinases, serine protease inhibitors, and neuro-inflammatory proteins such as amyloid precursor protein, chromogranin A, and glial fibrillary acidic protein. Compared to the filtered ALS-CSF mice, unfiltered ALS-CSF mice took longer to descend a pole (10 days post-injection, 11.14 seconds vs 14.25 seconds, p = 0.02) and explored less on an open field (one day post-injection, 21.81 m vs 16.83 m, p = 0.0004).
We demonstrated the ability to filter proteins from the CSF of ALS patients and identified potentially pathologic proteins that were reduced in quantity. Additionally, we demonstrated the ability of unfiltered ALS-CSF to induce motor deficits in mice on the pole descent and open field tests and showed that filtration could prevent this deficit. Given the lack of effective treatments for ALS, this could be a novel solution for patients suffering from this deadly and irreversible condition. |
doi_str_mv | 10.7759/cureus.32980 |
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We filtered the CSF from 11 ALS patients via 100 kilodaltons (kD) molecular weight cut-off filters. We used mass spectrometry-based discovery proteomics workflows to compare protein abundances before and after filtration. To test the effects of CSF filtration on motor function, we injected groups of mice with saline, filtered ALS-CSF, or unfiltered ALS-CSF (n=12 per group) and assessed motor function via pole descent and open field tests.
We identified proteins implicated in ALS pathogenesis and showed that these were removed in significant amounts in our workflow. Key filtered proteins included complement proteins, chitinases, serine protease inhibitors, and neuro-inflammatory proteins such as amyloid precursor protein, chromogranin A, and glial fibrillary acidic protein. Compared to the filtered ALS-CSF mice, unfiltered ALS-CSF mice took longer to descend a pole (10 days post-injection, 11.14 seconds vs 14.25 seconds, p = 0.02) and explored less on an open field (one day post-injection, 21.81 m vs 16.83 m, p = 0.0004).
We demonstrated the ability to filter proteins from the CSF of ALS patients and identified potentially pathologic proteins that were reduced in quantity. Additionally, we demonstrated the ability of unfiltered ALS-CSF to induce motor deficits in mice on the pole descent and open field tests and showed that filtration could prevent this deficit. Given the lack of effective treatments for ALS, this could be a novel solution for patients suffering from this deadly and irreversible condition.</description><identifier>ISSN: 2168-8184</identifier><identifier>EISSN: 2168-8184</identifier><identifier>DOI: 10.7759/cureus.32980</identifier><identifier>PMID: 36712738</identifier><language>eng</language><publisher>United States: Cureus Inc</publisher><subject>Amyotrophic lateral sclerosis ; Biobanks ; Cerebrospinal fluid ; Guillain-Barre syndrome ; Mass spectrometry ; Medical research ; Patients ; Peptides ; Proteins ; Proteomics ; Review boards ; Scientific imaging</subject><ispartof>Curēus (Palo Alto, CA), 2022-12, Vol.14 (12), p.e32980-e32980</ispartof><rights>Copyright © 2022, Venkatraman et al.</rights><rights>Copyright © 2022, Venkatraman et al. This work is published under https://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c287t-87c446c7b3875946da5d5862c366bb7cdf4a1b7d49c0b015ed679390e0c1e55f3</citedby><cites>FETCH-LOGICAL-c287t-87c446c7b3875946da5d5862c366bb7cdf4a1b7d49c0b015ed679390e0c1e55f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36712738$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Venkatraman, Vishal</creatorcontrib><creatorcontrib>Filiano, Anthony J</creatorcontrib><creatorcontrib>Xu, Li</creatorcontrib><creatorcontrib>Collins, Leonard</creatorcontrib><creatorcontrib>Luo, Emily</creatorcontrib><creatorcontrib>Ripple, Katelyn M</creatorcontrib><creatorcontrib>de Castro, George C</creatorcontrib><creatorcontrib>Boua, Jane-Valeriane K</creatorcontrib><creatorcontrib>Marius, Choiselle</creatorcontrib><creatorcontrib>Giamberardino, Charles</creatorcontrib><creatorcontrib>Lad, Shivanand P</creatorcontrib><creatorcontrib>Islam Williams, Taufika</creatorcontrib><creatorcontrib>Bereman, Michael S</creatorcontrib><creatorcontrib>Bedlack, Richard S</creatorcontrib><title>Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model</title><title>Curēus (Palo Alto, CA)</title><addtitle>Cureus</addtitle><description>Cerebrospinal fluid (CSF) has been implicated in amyotrophic lateral sclerosis (ALS) due to its ability to spread inflammatory proteins throughout the nervous system. We hypothesized that filtration of the CSF could remove pathogenic proteins and prevent them from altering motor phenotypes in a mouse model.
We filtered the CSF from 11 ALS patients via 100 kilodaltons (kD) molecular weight cut-off filters. We used mass spectrometry-based discovery proteomics workflows to compare protein abundances before and after filtration. To test the effects of CSF filtration on motor function, we injected groups of mice with saline, filtered ALS-CSF, or unfiltered ALS-CSF (n=12 per group) and assessed motor function via pole descent and open field tests.
We identified proteins implicated in ALS pathogenesis and showed that these were removed in significant amounts in our workflow. Key filtered proteins included complement proteins, chitinases, serine protease inhibitors, and neuro-inflammatory proteins such as amyloid precursor protein, chromogranin A, and glial fibrillary acidic protein. Compared to the filtered ALS-CSF mice, unfiltered ALS-CSF mice took longer to descend a pole (10 days post-injection, 11.14 seconds vs 14.25 seconds, p = 0.02) and explored less on an open field (one day post-injection, 21.81 m vs 16.83 m, p = 0.0004).
We demonstrated the ability to filter proteins from the CSF of ALS patients and identified potentially pathologic proteins that were reduced in quantity. Additionally, we demonstrated the ability of unfiltered ALS-CSF to induce motor deficits in mice on the pole descent and open field tests and showed that filtration could prevent this deficit. Given the lack of effective treatments for ALS, this could be a novel solution for patients suffering from this deadly and irreversible condition.</description><subject>Amyotrophic lateral sclerosis</subject><subject>Biobanks</subject><subject>Cerebrospinal fluid</subject><subject>Guillain-Barre syndrome</subject><subject>Mass spectrometry</subject><subject>Medical research</subject><subject>Patients</subject><subject>Peptides</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Review boards</subject><subject>Scientific imaging</subject><issn>2168-8184</issn><issn>2168-8184</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpdkUFrGzEQhUVIqIPjW89BkEsOdSKttCvt0Th1GnCJoS09LlppFitoV1tJe_Avyd-tGjul9DIzDN88hvcQ-kjJnRBlfa-nAFO8Y0UtyRm6LGgll5JKfv7PPEOLGF8IIZSIggjyAc1YJWghmLxErxvrEgQweJ1rG3wc7aAc3rjJGrwJvsc7lSwMKeKfNu3xqj_4FPy4txpvVT7N8DftIF_aiB9sHJ06RKwGvDoJ74JP4HvIO4NXXQc6a331yQe828Pg02EEbAes8nKKkKsBd4UuOuUiLE59jn5sPn9ff1lunx-f1qvtUhdSpKUUmvNKi5bJbAevjCpNKatCs6pqW6FNxxVtheG1Ji2hJZhK1KwmQDSFsuzYHN0edcfgf00QU9PbqME5NUD-pimEoETyWvCM3vyHvvgpZLOOVMF5LVmmPh0pnR2JAbpmDLZX4dBQ0vzJrDlm1rxllvHrk-jU9mD-wu8Jsd-YpZRr</recordid><startdate>20221226</startdate><enddate>20221226</enddate><creator>Venkatraman, Vishal</creator><creator>Filiano, Anthony J</creator><creator>Xu, Li</creator><creator>Collins, Leonard</creator><creator>Luo, Emily</creator><creator>Ripple, Katelyn M</creator><creator>de Castro, George C</creator><creator>Boua, Jane-Valeriane K</creator><creator>Marius, Choiselle</creator><creator>Giamberardino, Charles</creator><creator>Lad, Shivanand P</creator><creator>Islam Williams, Taufika</creator><creator>Bereman, Michael S</creator><creator>Bedlack, Richard S</creator><general>Cureus Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20221226</creationdate><title>Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model</title><author>Venkatraman, Vishal ; Filiano, Anthony J ; Xu, Li ; Collins, Leonard ; Luo, Emily ; Ripple, Katelyn M ; de Castro, George C ; Boua, Jane-Valeriane K ; Marius, Choiselle ; Giamberardino, Charles ; Lad, Shivanand P ; Islam Williams, Taufika ; Bereman, Michael S ; Bedlack, Richard S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c287t-87c446c7b3875946da5d5862c366bb7cdf4a1b7d49c0b015ed679390e0c1e55f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Amyotrophic lateral sclerosis</topic><topic>Biobanks</topic><topic>Cerebrospinal fluid</topic><topic>Guillain-Barre syndrome</topic><topic>Mass spectrometry</topic><topic>Medical research</topic><topic>Patients</topic><topic>Peptides</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Review boards</topic><topic>Scientific imaging</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Venkatraman, Vishal</creatorcontrib><creatorcontrib>Filiano, Anthony J</creatorcontrib><creatorcontrib>Xu, Li</creatorcontrib><creatorcontrib>Collins, Leonard</creatorcontrib><creatorcontrib>Luo, Emily</creatorcontrib><creatorcontrib>Ripple, Katelyn M</creatorcontrib><creatorcontrib>de Castro, George C</creatorcontrib><creatorcontrib>Boua, Jane-Valeriane K</creatorcontrib><creatorcontrib>Marius, Choiselle</creatorcontrib><creatorcontrib>Giamberardino, Charles</creatorcontrib><creatorcontrib>Lad, Shivanand P</creatorcontrib><creatorcontrib>Islam Williams, Taufika</creatorcontrib><creatorcontrib>Bereman, Michael S</creatorcontrib><creatorcontrib>Bedlack, Richard S</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Curēus (Palo Alto, CA)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Venkatraman, Vishal</au><au>Filiano, Anthony J</au><au>Xu, Li</au><au>Collins, Leonard</au><au>Luo, Emily</au><au>Ripple, Katelyn M</au><au>de Castro, George C</au><au>Boua, Jane-Valeriane K</au><au>Marius, Choiselle</au><au>Giamberardino, Charles</au><au>Lad, Shivanand P</au><au>Islam Williams, Taufika</au><au>Bereman, Michael S</au><au>Bedlack, Richard S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model</atitle><jtitle>Curēus (Palo Alto, CA)</jtitle><addtitle>Cureus</addtitle><date>2022-12-26</date><risdate>2022</risdate><volume>14</volume><issue>12</issue><spage>e32980</spage><epage>e32980</epage><pages>e32980-e32980</pages><issn>2168-8184</issn><eissn>2168-8184</eissn><abstract>Cerebrospinal fluid (CSF) has been implicated in amyotrophic lateral sclerosis (ALS) due to its ability to spread inflammatory proteins throughout the nervous system. We hypothesized that filtration of the CSF could remove pathogenic proteins and prevent them from altering motor phenotypes in a mouse model.
We filtered the CSF from 11 ALS patients via 100 kilodaltons (kD) molecular weight cut-off filters. We used mass spectrometry-based discovery proteomics workflows to compare protein abundances before and after filtration. To test the effects of CSF filtration on motor function, we injected groups of mice with saline, filtered ALS-CSF, or unfiltered ALS-CSF (n=12 per group) and assessed motor function via pole descent and open field tests.
We identified proteins implicated in ALS pathogenesis and showed that these were removed in significant amounts in our workflow. Key filtered proteins included complement proteins, chitinases, serine protease inhibitors, and neuro-inflammatory proteins such as amyloid precursor protein, chromogranin A, and glial fibrillary acidic protein. Compared to the filtered ALS-CSF mice, unfiltered ALS-CSF mice took longer to descend a pole (10 days post-injection, 11.14 seconds vs 14.25 seconds, p = 0.02) and explored less on an open field (one day post-injection, 21.81 m vs 16.83 m, p = 0.0004).
We demonstrated the ability to filter proteins from the CSF of ALS patients and identified potentially pathologic proteins that were reduced in quantity. Additionally, we demonstrated the ability of unfiltered ALS-CSF to induce motor deficits in mice on the pole descent and open field tests and showed that filtration could prevent this deficit. Given the lack of effective treatments for ALS, this could be a novel solution for patients suffering from this deadly and irreversible condition.</abstract><cop>United States</cop><pub>Cureus Inc</pub><pmid>36712738</pmid><doi>10.7759/cureus.32980</doi><oa>free_for_read</oa></addata></record> |
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subjects | Amyotrophic lateral sclerosis Biobanks Cerebrospinal fluid Guillain-Barre syndrome Mass spectrometry Medical research Patients Peptides Proteins Proteomics Review boards Scientific imaging |
title | Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model |
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