ArticleAlzheimer's research & therapy2026
Sequential associations of myelin dysfunction with Aβ and Tau pathology in Alzheimer's disease: a dynamic myelin perturbation.
Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMyelin dysfunction has emerged as a potentially pivotal factor in Alzheimer's disease (AD); however, its temporal dynamics and relationship with hallmark pathological processes remain incompletely understood. This study aimed to investigate dynamic demyelination and its association with the progression of Aβ and Tau pathology in AD.
methodsA total of 1,237 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with 18F-florbetapir (FBP) PET imaging were included. White matter SUVR (WM SUVR), defined as the adjusted FBP signal in white matter, was used as a proxy measure of myelin integrity. Cross-sectional and longitudinal analyses were conducted to examine associations between WM SUVR and AD progression, as well as AD-related biomarkers. Using cortical Aβ accumulation as a temporal reference, we further evaluated two-year changes in cortical Aβ and cumulative Tau PET signals in individuals with and without reduced myelin integrity (WM - vs. WM + uptake).
resultsWM SUVR demonstrated a gradual decline with advancing AD severity. Lower WM SUVR was associated with changes in Aβ
conclusionsProgressive myelin dysfunction is observed across the course of AD as a notable perturbation within neurodegenerative processes. Early alterations in myelin integrity are associated with subsequent Aβ accumulation, whereas later changes coincide with increased Tau aggregation. These findings support a conceptual framework in which myelin degeneration shows temporally structured associations with AD pathology and may serve as a sensitive marker of vulnerability, particularly in early disease stages.
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