Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults
Evidence suggests that lightly myelinated cortical regions are vulnerable to aging and Alzheimer’s disease (AD). However, it remains unknown whether plasma markers of amyloid and neurodegeneration are related to deficits in intracortical myelin content, and whether this relationship, in turn, is ass...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.896848/full |
| _version_ | 1811245688947736576 |
|---|---|
| author | Marina Fernandez-Alvarez Marina Fernandez-Alvarez Mercedes Atienza Mercedes Atienza Fatima Zallo Carlos Matute Carlos Matute Estibaliz Capetillo-Zarate Estibaliz Capetillo-Zarate Estibaliz Capetillo-Zarate Jose L. Cantero Jose L. Cantero |
| author_facet | Marina Fernandez-Alvarez Marina Fernandez-Alvarez Mercedes Atienza Mercedes Atienza Fatima Zallo Carlos Matute Carlos Matute Estibaliz Capetillo-Zarate Estibaliz Capetillo-Zarate Estibaliz Capetillo-Zarate Jose L. Cantero Jose L. Cantero |
| author_sort | Marina Fernandez-Alvarez |
| collection | DOAJ |
| description | Evidence suggests that lightly myelinated cortical regions are vulnerable to aging and Alzheimer’s disease (AD). However, it remains unknown whether plasma markers of amyloid and neurodegeneration are related to deficits in intracortical myelin content, and whether this relationship, in turn, is associated with altered patterns of resting-state functional connectivity (rs-FC). To shed light into these questions, plasma levels of amyloid-β fragment 1–42 (Aβ1–42) and neurofilament light chain (NfL) were measured using ultra-sensitive single-molecule array (Simoa) assays, and the intracortical myelin content was estimated with the ratio T1-weigthed/T2-weighted (T1w/T2w) in 133 cognitively normal older adults. We assessed: (i) whether plasma Aβ1–42 and/or NfL levels were associated with intracortical myelin content at different cortical depths and (ii) whether cortical regions showing myelin reductions also exhibited altered rs-FC patterns. Surface-based multiple regression analyses revealed that lower plasma Aβ1–42 and higher plasma NfL were associated with lower myelin content in temporo-parietal-occipital regions and the insular cortex, respectively. Whereas the association with Aβ1–42 decreased with depth, the NfL-myelin relationship was most evident in the innermost layer. Older individuals with higher plasma NfL levels also exhibited altered rs-FC between the insula and medial orbitofrontal cortex. Together, these findings establish a link between plasma markers of amyloid/neurodegeneration and intracortical myelin content in cognitively normal older adults, and support the role of plasma NfL in boosting aberrant FC patterns of the insular cortex, a central brain hub highly vulnerable to aging and neurodegeneration. |
| first_indexed | 2024-04-12T14:42:12Z |
| format | Article |
| id | doaj.art-0a64722548744b8ba73e64098125a30d |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-12T14:42:12Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-0a64722548744b8ba73e64098125a30d2022-12-22T03:28:46ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-06-011410.3389/fnagi.2022.896848896848Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older AdultsMarina Fernandez-Alvarez0Marina Fernandez-Alvarez1Mercedes Atienza2Mercedes Atienza3Fatima Zallo4Carlos Matute5Carlos Matute6Estibaliz Capetillo-Zarate7Estibaliz Capetillo-Zarate8Estibaliz Capetillo-Zarate9Jose L. Cantero10Jose L. Cantero11Laboratory of Functional Neuroscience, Pablo de Olavide University, Seville, SpainNetwork Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainLaboratory of Functional Neuroscience, Pablo de Olavide University, Seville, SpainNetwork Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainDepartamento de Neurociencias, Achucarro Basque Center for Neuroscience, Universidad del País Vasco, Leioa, SpainNetwork Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainDepartamento de Neurociencias, Achucarro Basque Center for Neuroscience, Universidad del País Vasco, Leioa, SpainNetwork Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainDepartamento de Neurociencias, Achucarro Basque Center for Neuroscience, Universidad del País Vasco, Leioa, SpainIkerbasque, Basque Foundation for Science, Bilbao, SpainLaboratory of Functional Neuroscience, Pablo de Olavide University, Seville, SpainNetwork Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, SpainEvidence suggests that lightly myelinated cortical regions are vulnerable to aging and Alzheimer’s disease (AD). However, it remains unknown whether plasma markers of amyloid and neurodegeneration are related to deficits in intracortical myelin content, and whether this relationship, in turn, is associated with altered patterns of resting-state functional connectivity (rs-FC). To shed light into these questions, plasma levels of amyloid-β fragment 1–42 (Aβ1–42) and neurofilament light chain (NfL) were measured using ultra-sensitive single-molecule array (Simoa) assays, and the intracortical myelin content was estimated with the ratio T1-weigthed/T2-weighted (T1w/T2w) in 133 cognitively normal older adults. We assessed: (i) whether plasma Aβ1–42 and/or NfL levels were associated with intracortical myelin content at different cortical depths and (ii) whether cortical regions showing myelin reductions also exhibited altered rs-FC patterns. Surface-based multiple regression analyses revealed that lower plasma Aβ1–42 and higher plasma NfL were associated with lower myelin content in temporo-parietal-occipital regions and the insular cortex, respectively. Whereas the association with Aβ1–42 decreased with depth, the NfL-myelin relationship was most evident in the innermost layer. Older individuals with higher plasma NfL levels also exhibited altered rs-FC between the insula and medial orbitofrontal cortex. Together, these findings establish a link between plasma markers of amyloid/neurodegeneration and intracortical myelin content in cognitively normal older adults, and support the role of plasma NfL in boosting aberrant FC patterns of the insular cortex, a central brain hub highly vulnerable to aging and neurodegeneration.https://www.frontiersin.org/articles/10.3389/fnagi.2022.896848/fullagingAlzheimer’s diseaseintracortical myelinfunctional connectivityblood biomarkersamyloid-beta |
| spellingShingle | Marina Fernandez-Alvarez Marina Fernandez-Alvarez Mercedes Atienza Mercedes Atienza Fatima Zallo Carlos Matute Carlos Matute Estibaliz Capetillo-Zarate Estibaliz Capetillo-Zarate Estibaliz Capetillo-Zarate Jose L. Cantero Jose L. Cantero Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults Frontiers in Aging Neuroscience aging Alzheimer’s disease intracortical myelin functional connectivity blood biomarkers amyloid-beta |
| title | Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults |
| title_full | Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults |
| title_fullStr | Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults |
| title_full_unstemmed | Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults |
| title_short | Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults |
| title_sort | linking plasma amyloid beta and neurofilament light chain to intracortical myelin content in cognitively normal older adults |
| topic | aging Alzheimer’s disease intracortical myelin functional connectivity blood biomarkers amyloid-beta |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.896848/full |
| work_keys_str_mv | AT marinafernandezalvarez linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT marinafernandezalvarez linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT mercedesatienza linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT mercedesatienza linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT fatimazallo linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT carlosmatute linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT carlosmatute linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT estibalizcapetillozarate linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT estibalizcapetillozarate linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT estibalizcapetillozarate linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT joselcantero linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults AT joselcantero linkingplasmaamyloidbetaandneurofilamentlightchaintointracorticalmyelincontentincognitivelynormalolderadults |