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Summary
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Neurofilament light chain (NfL) levels correlate with brain aging, but white matter hyperintensities (WMH) mediate neurodegeneration, indicating vascular pathology drives brain changes in older adults.

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Area of Science:

  • Neurology
  • Biomarkers
  • Neuroimaging

Background:

  • Neurofilament light chain (NfL) is a potential biomarker for neurodegeneration.
  • The relationship between NfL, white matter hyperintensities (WMH), and neurodegeneration in non-demented older adults is not fully understood.
  • Vascular pathology's role as a mediator requires investigation.

Purpose of the Study:

  • To investigate the interplay between NfL, WMH, and neurodegeneration in non-demented older adults.
  • To determine if WMH mediates the association between NfL and neurodegeneration.
  • To clarify the role of vascular pathology in brain aging.

Main Methods:

  • Included 202 non-demented older adults from four longitudinal aging studies.
  • Measured NfL in blood samples and assessed neurodegeneration using deformation-based morphometry (DBM) via log Jacobian (LogJ) maps.
  • Analyzed white matter hyperintensities (WMH) volume from MRI scans and used voxel-wise linear regression to assess associations, adjusting for covariates.

Main Results:

  • NfL levels were associated with reduced brain tissue volume and ventricular enlargement.
  • A significant positive association was found between NfL levels and WMH burden.
  • WMH burden was strongly associated with neurodegeneration, and it mediated the relationship between NfL and neurodegeneration.

Conclusions:

  • NfL reflects both neurodegenerative and vascular aspects of brain aging.
  • Vascular pathology, indicated by WMH, plays a critical role in driving neurodegeneration.
  • These findings emphasize the importance of considering vascular factors in brain aging research.