Integrating Retrogenesis Theory to Alzheimer’s Disease Pathology: Insight from DTI-TBSS Investigation of the White Matter Microstructural Integrity

Figure 1

(a) Wallerian degeneration occurs as a secondary product of gray matter loss, while retrogenesis hypothesis outlines the degeneration of late-myelination fibers in neocortical areas. The Wallerian degeneration model postulates a posterior-anterior gradient of fibre degeneration (right side, arrows); the normal myelinisation occurs throughout the first life decades, beginning at dorsal brain and reaching neocortical areas at end stages (right side, arrows). According to the retrogenesis model, neocortical fibers are those more likely to suffer early degeneration by AD; (b) myelin breakdown and axonal damage are one of the key pathological mechanisms underlying white matter microscopic lesions (b). (c) A projection of the ellipse onto the three main axes (, , ) or eigenvectors. The main DTI indices of fractional anisotropy (FA) and axial (DA), radial (DR) and mean (MD) diffusivity are based on the eigenvector calculations (bottom).

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