Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease
Legend: Shown are representative axial slices depicting areas of significant relationship (color overlay) between myelin water fraction and sAPPβ/Aβ42 displayed on the group mean myelin water fraction map. Myelin water fraction was observed to be negatively related to levels of sAPPβ/Aβ42. Results are false discovery rate (FDR) corrected for multiple comparisons (p < .05).
Citation: 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. (2017). Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease. JAMA Neurology. 2017 Jan 1;74(1):41-49.
Abstract: Myelin and myelin-producing oligodendrocytes appear to be affected in Alzheimer’s disease (AD), but this is understudied in humans, particularly in the early stages of disease development. Together with collaborators at the Wisconsin Alzheimer’s Disease Research Center, and Andy Alexander at the Waisman Center, postdoctoral fellow Doug Dean III, assessed the relationship between amyloid abnormalities measured with cerebrospinal fluid biomarkers (CSF) and myelin alteration as assessed with MRI using the Multicomponent Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) technique. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers of AD across brain white matter in areas preferentially affected by the disease. The findings suggest amyloid pathology influences myelin and that myelin abnormalities may be an early feature of the disease process.
About the Lab: Bendlin’s work focuses on brain structure and function in middle and late age, especially in people with increased risk of developing AD due to parental family history, genotype and vascular risk factors. Understanding early brain changes in people who may go on to develop AD is expected to lead to earlier diagnosis, prevention, and the development of new therapies for AD. Her current projects use MRI as a tool to understand the effect of risk factors (parental family history, genotype, metabolic syndrome) on brain blood flow and structure. Additionally, she is funded to examine the relationship between cerebrospinal fluid biomarkers and brain structure to learn more about early mechanisms of brain damage in AD.