Work

Investigation of the myelin-amyloid interplay in Alzheimer’s disease: insights from novel dsCMA imaging in mouse and human brains

Year: 2026

Type: article

Abstract: Myelin deterioration impairs neural communication and may contribute to neurodegenerative diseases such as Alzheimer's disease (AD). However, the spatiotemporal relationship between myelin degeneration and AD pathology remains unclear. We developed a novel imaging method-double-scan Cyto- and myelo-architecture (dsCMA)-that integrates multi-fluorescent labeling of cytoarchitecture and pathological markers with brightfield myelin staining on the same tissue sections. Coupled with computational tools for automated detection and quantification of amyloid-beta (Aβ) plaques and myelinated axons, dsCMA enables systematic analysis of Aβ-myelin interactions in 5xFAD mice and postmortem human AD tissues. In mice, we identified progressive, region-specific myelin disruption associated with Aβ accumulation, particularly in the hippocampus and cortex. Human samples revealed variable Aβ-myelin spatial relationships across individuals and regions, with evidence supporting a potential myelin origin for some plaques. These findings offer new insights into Aβ-myelin interplay and establish dsCMA as a scalable platform for histopathological analysis in translational and longitudinal AD research.

Source: Acta Neuropathologica Communications

DOI: 10.1186/s40478-026-02317-8