Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer's disease supports retrogenesis

By N. Stricker, B. Schweinsburg, L. Delano-Wood, C. Wierenga, K. Bangen, K. Haaland, L. Frank, David P. Salmon, M. Bondi. NeuroImage, 2008

324 citations recorded by the source corpus.

The retrogenesis model of Alzheimer's disease (AD) posits that white matter (WM) degeneration follows a pattern that is the reverse of myelogenesis. Using diffusion tensor imaging (DTI) to test this model, we predicted greater loss of microstructural integrity in late-myelinating WM fiber pathways in AD patients than in healthy older adults, whereas differences in early-myelinating WM fiber pathways were not expected. We compared 16 AD patients and 14 demographically-matched healthy older adults with a whole-brain approach via tract-based spatial statistics (TBSS), and a region of interest (ROI) approach targeting early-myelinating (posterior limb of internal capsule, cerebral peduncles) and late-myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF]) fiber pathways. Permutation-based voxelwise analysis supported the retrogenesis model. There was significantly lower fractional anisotropy (FA) in AD patients compared to healthy older adults in late-myelinating but not early-myelinating pathways. These group differences appeared to be driven by loss of myelin integrity based on our finding of greater radial diffusion in AD than in healthy elderly. ROI analyses were generally in agreement with whole-brain findings, with significantly lower FA and increased radial diffusion in the ILF in the AD group. Consistent with the retrogenesis model, AD patients showed demonstrable changes in late-myelinating WM fiber pathways. Given greater change in the ILF than the SLF, wallerian degeneration secondary to cortical atrophy may also be a contributing mechanism. Knowledge of the pattern of WM microstructural changes in AD and its underlying mechanisms may contribute to earlier detection and intervention in at-risk groups.

Subfields: Physiology, Psychiatry and Mental health, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/f2e5ec1452b94ceb6e5d200eb57e99e4b8d2a759

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In Psychiatry and Mental health

Stephen M. Smith

In Radiology, Nuclear Medicine and Imaging

Citations in the corpus

Structural connectomics in brain diseases (2013, unknown): “This interpretation is in line with retrogenesis models of Alzheimer’s disease (Stricker et al., 2009), for which the degeneration of fiber tracts would follow an inverse path respect to the myelination process occurring during development, where association fibers develop later on (Hagmann et al.,…”
DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease (2011, background): “…(reviews in Bozzali and Cherubini, 2007; Chua et al., 2008; Hess, 2009), there have been few whole-brain voxel-wise studies in which no a priori hypothesis was made regarding anatomical localisation of white matter abnormalities (e.g. Rose et al., 2006; Teipel et al., 2007; Stricker et al., 2009).”
White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes (2018, unknown): “In addition, there is a particular susceptibility for demyelination in areas that are myelinated at older ages, a phenomenon referred to as “neuropathologic retrogenesis” [8, 12, 17, 66, 76].”