Baseline Amyloid and Tau Deposition Predict Distinct Patterns of Longitudinal White Matter Degeneration: A Diffusion MRI Investigation
Jenna K Blujus, Hwamee Oh- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Neuritic plaques with fibrillar beta‐amyloid (Aβ) peptides and tau‐protein neurofibrillary tangles are hallmark features of Alzheimer’s disease (AD) pathology. While concomitant differences in white matter (WM) integrity were found in association with Aβ deposition or tau pathology, a unique effect of each pathology on WM integrity remains unknown. In this study, we examined the unique effects of AD pathologies on WM integrity both cross‐sectionally and longitudinally.
Method
A total of 334 participants (188 cognitively normal (CN), 114 mild cognitive impairment, and 32 AD) was selected from the ADNI database, based on the availability of two timepoints of diffusion MRI (dMRI) data, and baseline amyloid and tau PET data. The dMRI data were processed using FSL’s TBSS pipeline to quantify the degree of fractional anisotropy (FA) and annualized FA change maps were created to measure voxel‐wise WM change over time. Baseline global amyloid SUVR values were converted to a centiloid scale. Baseline tau SUVRs were evaluated by Braak staging (I‐entorhinal, II‐hippocampal, III/IV‐limbic, V/VI‐neocortex). The associations between AD pathologies and cross‐sectional and longitudinal WM integrity were assessed by FSL’s randomise and cluster‐level correction, controlling for age and sex.
Result
Cross‐sectionally, baseline tau burden in Braak stages I, III/IV, and V/VI related to lower WM integrity, independent of Aβ, while there was no association between baseline Aβ and WM integrity, independent of tau. Longitudinally, limbic and neocortical tau at baseline uniquely predicted WM integrity loss across widespread regions, including left superior longitudinal fasciculus and the body and splenium of corpus callosum. Moreover, baseline Aβ burden significantly related to WM integrity loss across widespread regions, only when entorhinal and hippocampal tau was controlled for. Similar, but weaker, patterns of the associations between baseline AD pathology and longitudinal WM integrity loss were also found only within CN group.
Conclusion
These findings suggest distinctive associations between AD pathology and WM degeneration such that Aß exerts widespread deleterious effects on WM integrity primarily early in AD pathophysiology, whereas, once spreading to the neocortex, tau burden drives WM neurodegeneration. The distinctive downstream pathways associated with each AD pathology may underlie differential cognitive profiles across the disease stages.