The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.
Tau protein levels are lower in more highly myelinated cortical regions.
Tau spreading is reduced between cortical regions that are connected by more highly myelinated fiber tracts.
Myelin may offer protection against tau accumulation associated with Alzheimer's disease (AD).
Why This Matters
Tau protein deposition and spreading are clinically relevant hallmarks of AD.
Autopsy studies have suggested that tau protein accumulation favors brain regions with less myelin.
The spreading of tau protein among brain regions appears to favor regions that are functionally connected.
Quantitative correlation of myelin level with tau protein accumulation would help physicians to offer patient-specific prognoses.
Identification of myelin as a protective factor would implicate it as a possible therapeutic target for AD.
The 612-member study population comprised select, biomarker-characterized patients (with dementia and without dementia) from the Alzheimer's Disease Neuroimaging Initiative (ANDI) and the BioFINDER-1 study.
Data from cross-sectional tau-PET assessments and MRI-based myelin mapping were used to correlate region-specific levels of myelin and tau protein in the cerebral cortex.
Data from longitudinal tau-PET assessments, MRI-based myelin mapping, and MRI-based structural and functional connectivity mapping were used to correlate tau protein changes in functionally paired regions with the myelin level of their connecting fiber tracts over 1 to 4 years.
Regions of interest with higher myelin water fractions had significantly lower tau-PET scores (rho = -0.267, P < .001 for the ANDI cohort; and rho = -0.175, P = .013 for the BioFINDER-1 cohort).
Linear regression analysis, testing the association of functional connectivity, fiber tract myelination, and covariance of tau-PET scores between linked brain regions, demonstrated a significant association (β = -0.185 and β = -0.166 for the respective cohorts; P < .001 for both cohorts), with more myelinated tracts showing a lesser association with tau covariance.
Among cognitively normal patients who lacked AD biomarkers, there was no significant correlation between regional myelin and tau-PET levels (rho = -0.13, P = .067; and rho = 0.027, P = .7 for the respective cohorts) or among fiber tract connectivity, fiber tract myelination, and tau covariance (β = 0.027, P = .39; and β = -0.026, P = .43 for the respective cohorts).
Sensitivity analyses that incorporated amyloid-PET assessments showed that the study results remained significant when amyloid-PET scores were controlled (P ≥ .005) and were therefore independent of amyloid beta levels.
Although MRI-based measurement of myelin can be confounded by iron content, myelin water imaging (used in this study) is demonstrably superior to other MRI measures in accurately assessing myelin levels.
An imaging template derived from healthy persons protected the MRI analysis from pathologic alterations in iron that could otherwise obfuscate the data.
This study did not track myelin changes over time, although in previous studies, demyelination has been associated with tau fibrils, and it is hypothesized that this association is causal.
Next steps include exploration of myelin's mechanism of protection, including the possibility that in less-myelinated regions, which are prone to myelin damage, remyelination activity initiates tau pathology.
Understanding of the mechanism of protection would support the development of myelin-targeted therapies.
The study was funded by the German Center for Neurodegenerative Diseases and by a grant from the Deutsche Forschungsgemeinschaft.
The ANDI is funded by the National Institute on Aging and by the National Institute of Biomedical Imaging and Bioengineering; participation in this study was supported by grants from the National Institutes of Health and the Department of Defense.
The ANDI receives funding from the Canadian Institutes of Health Research to support clinical sites in Canada.
The ANDI is also supported by contributions from the following, facilitated by the Foundation for the National Institutes of Health: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc; Cogstate; Eisai Inc; Elan Pharmaceuticals, Inc; Eli Lilly and Company; Eurolmmun; F. Hoffman-La Roche Ltd and its affiliated company Genentech, Inc; Fujirebio; GE Healthcare; IXICO Ltd; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co, Inc; Meso Scale Diagnostics, LLC; NeuroRX Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics.
This is a summary of a preprint research study, "Higher Levels of Myelin Are Associated With Higher Resistance Against Tau Pathology in Alzheimer’s Disease," written by Anna Rubinski from the Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilian University, Munich, Germany, and colleagues and published on medRxiv.org. It is provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.
Lead Image: Brand X/Getty Images
Cite this: Marisa DeNoble Loeffler. In Alzheimer's Disease, Myelin May Protect Against Tau Pathology - Medscape - Mar 16, 2022.