Just as certain areas of a city may be more susceptible to wear and tear, some parts of our brains are also more vulnerable to aging and neurodegenerative diseases like Alzheimer’s. Scientists wanted to understand whether plasma markers for amyloid beta and neurodegeneration could be linked to deficits in intracortical myelin content, a protective layer in the brain. Using sensitive assays to measure these plasma markers, researchers found that lower levels of amyloid beta and higher levels of neurofilament light chain were associated with lower myelin content in different regions of the brain. Interestingly, this relationship varied depending on the cortical depth, suggesting the complex nature of brain changes. Moreover, individuals with higher levels of neurofilament light chain showed altered patterns of resting-state functional connectivity between important brain hubs. These findings provide valuable insights into the relationship between plasma markers, brain myelin, and functional connectivity in cognitively normal older adults, potentially opening doors for early detection and intervention strategies for neurodegenerative diseases. To learn more about this fascinating research, be sure to check out the full article!

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.

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