Dean DC 3rd, Hurley SA, Kecskemeti SR, O'Grady JP, Canda C, Davenport-Sis NJ, Carlsson CM, Zetterberg H, Blennow K, Asthana S, Sager MA, Johnson SC, Alexander AL, Bendlin BB. Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease. JAMA Neurol. 2017 Jan 1;74(1):41-49. PubMed.
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Medical University of South Carolina
Age is the greatest risk factor for late-onset Alzheimer’s disease, which accounts for at least 95 percent of all incident cases. Given that white matter microstructure is strongly correlated with age, it stands to reason that age-related changes in this non-neuronal tissue may contribute to the pathogenesis of Alzheimer’s disease.
In their paper, Dr. Dean and colleagues tested this hypothesis by correlating brain MRI estimates of myelin content (Myelin Water Fraction [MWF], R1, R2) and CSF measurements of amyloid and tau in a sample of cognitively asymptomatic adults enriched for AD risk. In addition to corroborating the known correlation between myelin and age, they reported that diminished myelin was associated with lower Aβ42 and higher tau (Ttau, Ptau181), tau-Aβ ratios (Ttau/Aβ42, Ptau181/Aβ42), and soluble APP (sAPPβ, sAPPβ/Aβ42), and that elevated tau-Aβ ratios mediate accelerated age-related myelin loss. These voxelwise correlations were localized to many white matter regions implicated in previous work on white matter changes in aging and Alzheimer’s disease.
Their work demonstrates how myelin is not simply a bystander in this disease about which most research has been woefully over-focused on a handful of proteins and one cell type. These meaningful associations, albeit correlative, exemplify the clinical translation of our growing knowledge of neuron-glia interactions in the basic sciences. As a field we can no longer afford to be wedded to such circumscribed hypotheses of how Alzheimer’s disease begins and progresses, especially in the face of such data. Their work reminds us of what we in the field know all too well—that Alzheimer’s disease, much like the person it afflicts, is complex, multifaceted, and changing with age.
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