RT Journal Article
T1 Linking plasma amyloid beta and neurofilament light chain to intracortical myelin content in cognitively normal older adults
A1 Fernández Álvarez, Marina
A1 Atienza, Mercedes
A1 Zallo. Fátima, 
A1 Matute, Carlos
A1 Capetillo-Zarate, Estibaliz
A1 Cantero Lorente, José Luis
K1 Aging
K1 Alzheimer’s disease
K1 Intracortical myelin
K1 Functional connectivity
K1 Blood biomarkers
K1 Amyloidbeta
K1 Neurofilament light
AB 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.
PB Frontiers
YR 2022
FD 2022-06-17
LK https://hdl.handle.net/10433/22767
UL https://hdl.handle.net/10433/22767
LA en
NO Fernandez-Alvarez, M., Atienza, M., Zallo, F., Matute, C., Capetillo-Zarate, E., & Cantero, J. L. (2022). Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults. Frontiers in Aging Neuroscience, 14. https://www.frontiersin.org/article/10.3389/fnagi.2022.896848
NO Laboratory of Functional Neuroscience, Pablo de Olavide University, Seville, Spain
NO Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
NO Departamento de Neurociencias, Achucarro Basque Center for Neuroscience, Universidad del País Vasco, Leioa, Spain
NO Ikerbasque, Basque Foundation for Science, Bilbao, Spain
DS RIO
RD Apr 23, 2026