Min J, Rouanet J, Martini AC, Nashiro K, Yoo HJ, Porat S, Cho C, Wan J, Cole SW, Head E, Nation DA, Thayer JF, Mather M. Modulating heart rate oscillation affects plasma amyloid beta and tau levels in younger and older adults. Sci Rep. 2023 Mar 9;13(1):3967. PubMed.

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  1. I must commend these investigators for integrating plasma AD biomarkers into their study of a behavioral intervention. That they saw changes in these biomarkers with this relatively mild intervention is quite interesting and exciting. Interpreting those changes is a more complex issue. While there is a decrease in plasma Aβ, it's unclear if that is due to decreased production in the brain, increased proteolysis, or decreased clearance from the brain to the blood.

    The link to noradrenergic function, which seems a bit tenuous, implicates the glymphatic system. However, one might expect to see higher plasma Aβ levels with increased glymphatic function and clearance from brain to blood. Moreover, the increase in p-tau levels in plasma could be interpreted as a negative. The addition of CSF biomarkers might clarify some of these issues in the future. Despite these questions, it's certainly a thought-provoking study.

    View all comments by Erik Musiek

  2. The role of the noradrenergic system in the pathogenesis and progression of Alzheimer's disease has gained increasing attention in recent years. This clinical trial study demonstrated that by simulating vagus nerve pathways through heart rate variability feedback, there were observable changes in the levels of amyloid and tau in plasma. It would be valuable to additionally investigate changes in these biomarkers in cerebrospinal fluid (CSF).

    Nonetheless, this evidence in living people supports the idea of a causal relationship between noradrenergic activity and the regulation of Alzheimer’s disease hallmarks.

    View all comments by Qin Wang

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