Higher myelination of grey matter and white matter is associated with lower tau spreading and tau‐associated cortical thinning in Alzheimer's. (December 2021) - Rubinski, Anna
Abstract: Background: Myelination of axons in the grey matter (GM) and axonal connections may modulate the spreading of brain pathologies such as pathologic tau. Here, we tested for the first time whether MRI‐assessed myelination in the GM and white matter (WM) is associated with tau‐PET assessed spreading of pathologic tau between connected brain regions. We hypothesized that 1) higher myelination of WM connections is associated with lower tau‐PET in the connected regions and 2) higher myelination of GM is associated with higher resilience against the effect of tau on GM. Method: We included AV1451‐tau‐PET from 202 amyloid‐PET positive (Aβ+) asymptomatic and symptomatic individuals from ADNI. Using a neocortical 200‐ROI brain‐parcellation atlas, we obtained regional tau‐PET SUVR and cortical thickness. Resting‐state fMRI functional connectivity (FC) and DWI‐based fiber‐tracts between the 200 ROIs were assessed in 100 individuals from the human connectome project (HCP). Next, we applied the 200 GM‐ROIs and fiber‐tract streamlines to a myelin‐water‐imaging atlas in healthy individuals (Liu et al., JON, 2019) to assess the myelin water fraction (MWF) in GM‐ROIs and their WM connections. Using linear regression, we assessed the associations between MWF, FC and tau‐PET, as well as the interaction between MWF and tau‐PET on cortical thickness. Result: We found that higher MWF (i.e. higher myelin) in GM‐ROIs was associated with lower tau‐PET in corresponding ROIs (Figure 1, β=‐0.38, p<0.001). Using spatial regression, we found that for connections with lower MWF, the association between higher FC and higher tau‐PET was stronger (interaction MWF x FC on tau‐PET, Figure 2), suggesting that lower WM myelination facilitates the spreading of tau along connected regions. Lastly, the association between tau‐PET and cortical thinning in GM‐ROIs was attenuated at higher MWF in the corresponding GM‐ROIs (Figure 3, β=0.025, p<0.001), suggesting that higher GM myelination is associated with higher resilience against the effect of tau‐PET on GM atrophy. Conclusion: Higher myelination of the GM and WM is associated with lower regional susceptibility to pathologic tau and higher resilience against effects of tau on GM integrity.