Assessment of myelin in Alzheimer’s by a R1 and the relationship to amyloid burden

Background Alzheimer’s disease (AD) is well known as a grey matter disorder, characterized by substantial and progressive neurodegeneration. However, less is known about myelin loss in AD, particularly as the disease progresses in severity. To gain a better insight on the role of myelin over the clinical and biologic progression of AD, we tested for differences in quantitative relaxometry R1, a metric sensitive to brain myelin, among individuals who were cognitively unimpaired (CU), diagnosed with mild cognitive impairment (MCI), and diagnosed with AD, in addition to testing for associations between R1 and amyloid PET. Understanding the course of myelin injury in disease progression is expected to address the gap in knowledge about the trajectory of myelin alterations in AD. Methods Participants from the Alzheimer’s Disease Connectome Project underwent T1‐weighted (T1w) MPnRAGE with motion‐correction and amyloid imaging with [11C]PiB PET. Composite T1w images and R1 maps were reconstructed at 1mm isotropic resolution. T1w scans were bias‐field corrected and denoised before undergoing tissue segmentation. R1 was sampled and bilaterally averaged across cortical‐adjacent white matter (WM). An average WM‐R1 was generated for each participant by calculating the mean of cortical regions R1. MANOVA and regression analyses were used to analyze the difference and relationship between each group’s WM‐R1 and PiB‐Index. Result The three groups showed an association with PiB‐Index and WM‐R1, Pillai’s Trace = 0.28, F(4, 110) = 4.56, p<0.01. Participants with AD showed higher amyloid and lower WM‐R1. In contrast, UC and MCI participants showed lower amyloid and WM‐R1. A significant correlation was found in individuals with AD wherein amyloid burden was positively correlated with WM‐R1 across the whole brain, R 2 = 0.64, F(1, 6) = 10.99, p = 0.016. Conclusion Our findings indicate myelin differences by clinical status, in addition to relationships between amyloid and R1 indices of myelin. While AD was associated with lower myelin as indexed by R1, we unexpectedly found that higher cortical amyloid in AD was associated with higher myelin indexed by R1, suggesting an increase in myelination as AD progresses. Overall, lower myelin in clinical AD, accompanied by the higher myelin with greater amyloid burden suggests possible reparative mechanisms in response to neurodegeneration in AD.