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

N H Stricker1, B C Schweinsburg, L Delano-Wood

  • 1New Mexico VA Healthcare System, USA.

Neuroimage
|December 23, 2008
PubMed

Insights

Alzheimer's disease (AD) causes white matter (WM) degeneration in late-myelinating pathways, supporting the retrogenesis model. Early-myelinating pathways showed no significant changes in AD patients compared to healthy adults.

Area of Science:

  • Neuroscience
  • Neurology
  • Radiology

Background:

  • Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline.
  • The retrogenesis model proposes that white matter (WM) degeneration in AD mirrors the reverse of normal myelogenesis.
  • Understanding WM changes is crucial for early AD detection and intervention.

Purpose of the Study:

  • To test the retrogenesis model of AD using diffusion tensor imaging (DTI).
  • To investigate microstructural integrity differences in early- and late-myelinating WM pathways between AD patients and healthy adults.

Main Methods:

  • Employed diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) for whole-brain analysis.
  • Utilized region of interest (ROI) analysis targeting specific early- (posterior limb of internal capsule, cerebral peduncles) and late-myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF]) fiber pathways.
  • Compared 16 AD patients with 14 demographically-matched healthy older adults.

Main Results:

  • Significantly lower fractional anisotropy (FA) was observed in late-myelinating WM pathways in AD patients compared to controls.
  • No significant differences in FA were found in early-myelinating pathways between the groups.
  • Increased radial diffusion in AD patients suggested myelin integrity loss, particularly in the ILF.

Conclusions:

  • Findings support the retrogenesis model, indicating that AD preferentially affects late-myelinating WM pathways.
  • Myelin degeneration in late-myelinating tracts is a key feature of AD's WM pathology.
  • Wallerian degeneration secondary to cortical atrophy may also contribute to WM changes in AD.

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