Loading…
Glymphatic system clearance and Alzheimer's disease risk: a CSF proteome-wide study
The emerging evidence of the role of the glymphatic system (GS) in Alzheimer's disease (AD) provides new opportunities for intervention from the earliest stages of the disease. The aim of the study is to evaluate the efficacy of GS in AD to identify new disease biomarkers. We performed a two-st...
Saved in:
| Published in: | Alzheimer's research & therapy 2025-01, Vol.17 (1), p.31-13, Article 31 |
|---|---|
| Main Authors: | , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | |
|---|---|
| cites | cdi_FETCH-LOGICAL-c3321-acb63dba40de471ea606acbdc2fab9d543cf671869d831f17ebd7d34c7471f1d3 |
| container_end_page | 13 |
| container_issue | 1 |
| container_start_page | 31 |
| container_title | Alzheimer's research & therapy |
| container_volume | 17 |
| creator | Cullell, Natalia Caruana, Giovanni Elias-Mas, Andrea Delgado-Sanchez, Ariane Artero, Cristina Buongiorno, Maria Teresa Almería, Marta Ray, Nicola J Correa, Sonia A L Krupinski, Jerzy |
| description | The emerging evidence of the role of the glymphatic system (GS) in Alzheimer's disease (AD) provides new opportunities for intervention from the earliest stages of the disease. The aim of the study is to evaluate the efficacy of GS in AD to identify new disease biomarkers.
We performed a two-stage proteomic study to evaluate the GS health using intravenous gadolinium-based contrast agent (GBCA) with serial T1 3T magnetic resonance imaging (MRI) in individuals with amnestic mild cognitive impairment (aMCI). In Stage 1 (evaluated in the Cohort 1 of aMCI participants (n = 11)), we correlated the levels of 7K cerebrospinal fluid (CSF) proteins (estimated by SOMAscan) with GS health in 78 Freesurfer-segmented brain regions of interest (ROIs).
A total of seven different proteins were significantly associated with GS health (p-value |
| doi_str_mv | 10.1186/s13195-024-01612-7 |
| format | article |
| fullrecord | <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_656ffa0cc4bf485891bdaeb1c29a92e8</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A825847736</galeid><doaj_id>oai_doaj_org_article_656ffa0cc4bf485891bdaeb1c29a92e8</doaj_id><sourcerecordid>A825847736</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3321-acb63dba40de471ea606acbdc2fab9d543cf671869d831f17ebd7d34c7471f1d3</originalsourceid><addsrcrecordid>eNpVkk9v1DAQxSMEoqXwBTignKCXQPwntsMFrVZtqVSJQ-FsTezJxsWJFzsBLZ8etylVe7I1fvObefIrirek_kiIEp8SYaRtqpryqiaC0Eo-K46JbFTVkpY9f3Q_Kl6ldFPXQlDFXxZHrFUtoVwcF9cX_jDuB5idKdMhzTiWxiNEmAyWMNly4_8O6EaMH1JpXUJIWEaXfn4uodxen5f7GGYMI1Z_nMUyzYs9vC5e9OATvrk_T4of52fft1-rq28Xl9vNVWUYo6QC0wlmO-C1RS4JgqhFrllDe-ha23BmeiGz0dYqRnoisbPSMm5kVvfEspPicuXaADd6H90I8aADOH1XCHGnIWZjHrVoRN9DbQzveq6a7L6zgB0xtIWWosqsLytrv3QjWoPTHME_gT59mdygd-G3JkQqwRqWCaf3hBh-LZhmPbpk0HuYMCxJMyJoIyWlt8Per9Id5N0GBD8PKfhldmFKeqNoo7iUTGQhXYUmhpQi9g8LkVrfZkCvGdA5A_ouA1rmpnePrTy0_P909g-Rwa3o</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3162577228</pqid></control><display><type>article</type><title>Glymphatic system clearance and Alzheimer's disease risk: a CSF proteome-wide study</title><source>PubMed (Medline)</source><source>Publicly Available Content Database</source><creator>Cullell, Natalia ; Caruana, Giovanni ; Elias-Mas, Andrea ; Delgado-Sanchez, Ariane ; Artero, Cristina ; Buongiorno, Maria Teresa ; Almería, Marta ; Ray, Nicola J ; Correa, Sonia A L ; Krupinski, Jerzy</creator><creatorcontrib>Cullell, Natalia ; Caruana, Giovanni ; Elias-Mas, Andrea ; Delgado-Sanchez, Ariane ; Artero, Cristina ; Buongiorno, Maria Teresa ; Almería, Marta ; Ray, Nicola J ; Correa, Sonia A L ; Krupinski, Jerzy</creatorcontrib><description>The emerging evidence of the role of the glymphatic system (GS) in Alzheimer's disease (AD) provides new opportunities for intervention from the earliest stages of the disease. The aim of the study is to evaluate the efficacy of GS in AD to identify new disease biomarkers.
We performed a two-stage proteomic study to evaluate the GS health using intravenous gadolinium-based contrast agent (GBCA) with serial T1 3T magnetic resonance imaging (MRI) in individuals with amnestic mild cognitive impairment (aMCI). In Stage 1 (evaluated in the Cohort 1 of aMCI participants (n = 11)), we correlated the levels of 7K cerebrospinal fluid (CSF) proteins (estimated by SOMAscan) with GS health in 78 Freesurfer-segmented brain regions of interest (ROIs).
A total of seven different proteins were significantly associated with GS health (p-value < 6.4 × 10
). The stronger correlations were identified for NSUN6, GRAAK, OLFML3, ACTN2, RUXF, SHPS1 and TIM-4. A pathway enrichment analysis revealed that the proteins associated with GS health were mainly implicated in neurodegenerative processes, immunity and inflammation. In Stage 2, we validated these proteomic results in a new cohort of aMCI participants (with and without evidence of AD pathology in CSF (aMCI(-) and aMCI/AD( +); n = 22 and 7, respectively) and healthy controls (n = 10). Proteomic prediction models were generated in each ROI. These were compared with demographic-only models for identifying participants with aMCI(-) and aMCI/AD( +) vs controls. This analysis was repeated to determine if the models could identify those with aMCI/AD( +) from both aMCI(-) and controls. The proteomic models were found to outperform the demographic-only models.
Our study identifies proteins linked with GS health and involved the immune system in aMCI participants.</description><identifier>ISSN: 1758-9193</identifier><identifier>EISSN: 1758-9193</identifier><identifier>DOI: 10.1186/s13195-024-01612-7</identifier><identifier>PMID: 39891246</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Aged ; Aged, 80 and over ; Alzheimer Disease - cerebrospinal fluid ; Alzheimer's disease ; Analysis ; Biomarkers - cerebrospinal fluid ; Brain - diagnostic imaging ; Brain - metabolism ; Brain - pathology ; Cerebrospinal fluid ; Cognitive Dysfunction - cerebrospinal fluid ; Cohort Studies ; Development and progression ; Female ; Glymphatic System ; Health aspects ; Humans ; Inflammation ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Mild cognitive impairment ; MRI ; Proteome - metabolism ; Proteomics ; Proteomics - methods ; Risk factors</subject><ispartof>Alzheimer's research & therapy, 2025-01, Vol.17 (1), p.31-13, Article 31</ispartof><rights>2025. The Author(s).</rights><rights>COPYRIGHT 2025 BioMed Central Ltd.</rights><rights>The Author(s) 2025 2025</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3321-acb63dba40de471ea606acbdc2fab9d543cf671869d831f17ebd7d34c7471f1d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786353/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786353/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27900,27901,36989,53765,53767</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39891246$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cullell, Natalia</creatorcontrib><creatorcontrib>Caruana, Giovanni</creatorcontrib><creatorcontrib>Elias-Mas, Andrea</creatorcontrib><creatorcontrib>Delgado-Sanchez, Ariane</creatorcontrib><creatorcontrib>Artero, Cristina</creatorcontrib><creatorcontrib>Buongiorno, Maria Teresa</creatorcontrib><creatorcontrib>Almería, Marta</creatorcontrib><creatorcontrib>Ray, Nicola J</creatorcontrib><creatorcontrib>Correa, Sonia A L</creatorcontrib><creatorcontrib>Krupinski, Jerzy</creatorcontrib><title>Glymphatic system clearance and Alzheimer's disease risk: a CSF proteome-wide study</title><title>Alzheimer's research & therapy</title><addtitle>Alzheimers Res Ther</addtitle><description>The emerging evidence of the role of the glymphatic system (GS) in Alzheimer's disease (AD) provides new opportunities for intervention from the earliest stages of the disease. The aim of the study is to evaluate the efficacy of GS in AD to identify new disease biomarkers.
We performed a two-stage proteomic study to evaluate the GS health using intravenous gadolinium-based contrast agent (GBCA) with serial T1 3T magnetic resonance imaging (MRI) in individuals with amnestic mild cognitive impairment (aMCI). In Stage 1 (evaluated in the Cohort 1 of aMCI participants (n = 11)), we correlated the levels of 7K cerebrospinal fluid (CSF) proteins (estimated by SOMAscan) with GS health in 78 Freesurfer-segmented brain regions of interest (ROIs).
A total of seven different proteins were significantly associated with GS health (p-value < 6.4 × 10
). The stronger correlations were identified for NSUN6, GRAAK, OLFML3, ACTN2, RUXF, SHPS1 and TIM-4. A pathway enrichment analysis revealed that the proteins associated with GS health were mainly implicated in neurodegenerative processes, immunity and inflammation. In Stage 2, we validated these proteomic results in a new cohort of aMCI participants (with and without evidence of AD pathology in CSF (aMCI(-) and aMCI/AD( +); n = 22 and 7, respectively) and healthy controls (n = 10). Proteomic prediction models were generated in each ROI. These were compared with demographic-only models for identifying participants with aMCI(-) and aMCI/AD( +) vs controls. This analysis was repeated to determine if the models could identify those with aMCI/AD( +) from both aMCI(-) and controls. The proteomic models were found to outperform the demographic-only models.
Our study identifies proteins linked with GS health and involved the immune system in aMCI participants.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - cerebrospinal fluid</subject><subject>Alzheimer's disease</subject><subject>Analysis</subject><subject>Biomarkers - cerebrospinal fluid</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Cerebrospinal fluid</subject><subject>Cognitive Dysfunction - cerebrospinal fluid</subject><subject>Cohort Studies</subject><subject>Development and progression</subject><subject>Female</subject><subject>Glymphatic System</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mild cognitive impairment</subject><subject>MRI</subject><subject>Proteome - metabolism</subject><subject>Proteomics</subject><subject>Proteomics - methods</subject><subject>Risk factors</subject><issn>1758-9193</issn><issn>1758-9193</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVkk9v1DAQxSMEoqXwBTignKCXQPwntsMFrVZtqVSJQ-FsTezJxsWJFzsBLZ8etylVe7I1fvObefIrirek_kiIEp8SYaRtqpryqiaC0Eo-K46JbFTVkpY9f3Q_Kl6ldFPXQlDFXxZHrFUtoVwcF9cX_jDuB5idKdMhzTiWxiNEmAyWMNly4_8O6EaMH1JpXUJIWEaXfn4uodxen5f7GGYMI1Z_nMUyzYs9vC5e9OATvrk_T4of52fft1-rq28Xl9vNVWUYo6QC0wlmO-C1RS4JgqhFrllDe-ha23BmeiGz0dYqRnoisbPSMm5kVvfEspPicuXaADd6H90I8aADOH1XCHGnIWZjHrVoRN9DbQzveq6a7L6zgB0xtIWWosqsLytrv3QjWoPTHME_gT59mdygd-G3JkQqwRqWCaf3hBh-LZhmPbpk0HuYMCxJMyJoIyWlt8Per9Id5N0GBD8PKfhldmFKeqNoo7iUTGQhXYUmhpQi9g8LkVrfZkCvGdA5A_ouA1rmpnePrTy0_P909g-Rwa3o</recordid><startdate>20250131</startdate><enddate>20250131</enddate><creator>Cullell, Natalia</creator><creator>Caruana, Giovanni</creator><creator>Elias-Mas, Andrea</creator><creator>Delgado-Sanchez, Ariane</creator><creator>Artero, Cristina</creator><creator>Buongiorno, Maria Teresa</creator><creator>Almería, Marta</creator><creator>Ray, Nicola J</creator><creator>Correa, Sonia A L</creator><creator>Krupinski, Jerzy</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20250131</creationdate><title>Glymphatic system clearance and Alzheimer's disease risk: a CSF proteome-wide study</title><author>Cullell, Natalia ; Caruana, Giovanni ; Elias-Mas, Andrea ; Delgado-Sanchez, Ariane ; Artero, Cristina ; Buongiorno, Maria Teresa ; Almería, Marta ; Ray, Nicola J ; Correa, Sonia A L ; Krupinski, Jerzy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3321-acb63dba40de471ea606acbdc2fab9d543cf671869d831f17ebd7d34c7471f1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - cerebrospinal fluid</topic><topic>Alzheimer's disease</topic><topic>Analysis</topic><topic>Biomarkers - cerebrospinal fluid</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Cerebrospinal fluid</topic><topic>Cognitive Dysfunction - cerebrospinal fluid</topic><topic>Cohort Studies</topic><topic>Development and progression</topic><topic>Female</topic><topic>Glymphatic System</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mild cognitive impairment</topic><topic>MRI</topic><topic>Proteome - metabolism</topic><topic>Proteomics</topic><topic>Proteomics - methods</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cullell, Natalia</creatorcontrib><creatorcontrib>Caruana, Giovanni</creatorcontrib><creatorcontrib>Elias-Mas, Andrea</creatorcontrib><creatorcontrib>Delgado-Sanchez, Ariane</creatorcontrib><creatorcontrib>Artero, Cristina</creatorcontrib><creatorcontrib>Buongiorno, Maria Teresa</creatorcontrib><creatorcontrib>Almería, Marta</creatorcontrib><creatorcontrib>Ray, Nicola J</creatorcontrib><creatorcontrib>Correa, Sonia A L</creatorcontrib><creatorcontrib>Krupinski, Jerzy</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Alzheimer's research & therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cullell, Natalia</au><au>Caruana, Giovanni</au><au>Elias-Mas, Andrea</au><au>Delgado-Sanchez, Ariane</au><au>Artero, Cristina</au><au>Buongiorno, Maria Teresa</au><au>Almería, Marta</au><au>Ray, Nicola J</au><au>Correa, Sonia A L</au><au>Krupinski, Jerzy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glymphatic system clearance and Alzheimer's disease risk: a CSF proteome-wide study</atitle><jtitle>Alzheimer's research & therapy</jtitle><addtitle>Alzheimers Res Ther</addtitle><date>2025-01-31</date><risdate>2025</risdate><volume>17</volume><issue>1</issue><spage>31</spage><epage>13</epage><pages>31-13</pages><artnum>31</artnum><issn>1758-9193</issn><eissn>1758-9193</eissn><abstract>The emerging evidence of the role of the glymphatic system (GS) in Alzheimer's disease (AD) provides new opportunities for intervention from the earliest stages of the disease. The aim of the study is to evaluate the efficacy of GS in AD to identify new disease biomarkers.
We performed a two-stage proteomic study to evaluate the GS health using intravenous gadolinium-based contrast agent (GBCA) with serial T1 3T magnetic resonance imaging (MRI) in individuals with amnestic mild cognitive impairment (aMCI). In Stage 1 (evaluated in the Cohort 1 of aMCI participants (n = 11)), we correlated the levels of 7K cerebrospinal fluid (CSF) proteins (estimated by SOMAscan) with GS health in 78 Freesurfer-segmented brain regions of interest (ROIs).
A total of seven different proteins were significantly associated with GS health (p-value < 6.4 × 10
). The stronger correlations were identified for NSUN6, GRAAK, OLFML3, ACTN2, RUXF, SHPS1 and TIM-4. A pathway enrichment analysis revealed that the proteins associated with GS health were mainly implicated in neurodegenerative processes, immunity and inflammation. In Stage 2, we validated these proteomic results in a new cohort of aMCI participants (with and without evidence of AD pathology in CSF (aMCI(-) and aMCI/AD( +); n = 22 and 7, respectively) and healthy controls (n = 10). Proteomic prediction models were generated in each ROI. These were compared with demographic-only models for identifying participants with aMCI(-) and aMCI/AD( +) vs controls. This analysis was repeated to determine if the models could identify those with aMCI/AD( +) from both aMCI(-) and controls. The proteomic models were found to outperform the demographic-only models.
Our study identifies proteins linked with GS health and involved the immune system in aMCI participants.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>39891246</pmid><doi>10.1186/s13195-024-01612-7</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1758-9193 |
| ispartof | Alzheimer's research & therapy, 2025-01, Vol.17 (1), p.31-13, Article 31 |
| issn | 1758-9193 1758-9193 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_656ffa0cc4bf485891bdaeb1c29a92e8 |
| source | PubMed (Medline); Publicly Available Content Database |
| subjects | Aged Aged, 80 and over Alzheimer Disease - cerebrospinal fluid Alzheimer's disease Analysis Biomarkers - cerebrospinal fluid Brain - diagnostic imaging Brain - metabolism Brain - pathology Cerebrospinal fluid Cognitive Dysfunction - cerebrospinal fluid Cohort Studies Development and progression Female Glymphatic System Health aspects Humans Inflammation Magnetic Resonance Imaging Male Middle Aged Mild cognitive impairment MRI Proteome - metabolism Proteomics Proteomics - methods Risk factors |
| title | Glymphatic system clearance and Alzheimer's disease risk: a CSF proteome-wide study |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-24T04%3A03%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Glymphatic%20system%20clearance%20and%20Alzheimer's%20disease%20risk:%20a%20CSF%20proteome-wide%20study&rft.jtitle=Alzheimer's%20research%20&%20therapy&rft.au=Cullell,%20Natalia&rft.date=2025-01-31&rft.volume=17&rft.issue=1&rft.spage=31&rft.epage=13&rft.pages=31-13&rft.artnum=31&rft.issn=1758-9193&rft.eissn=1758-9193&rft_id=info:doi/10.1186/s13195-024-01612-7&rft_dat=%3Cgale_doaj_%3EA825847736%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c3321-acb63dba40de471ea606acbdc2fab9d543cf671869d831f17ebd7d34c7471f1d3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3162577228&rft_id=info:pmid/39891246&rft_galeid=A825847736&rfr_iscdi=true |