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Biomarkers.

Annegret Habich1, Bastiaan G J van Tol2, Milan Nemy3,4

  • 1Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary

Brain connections to the amygdala predict neurodegeneration in dementia with Lew bodies (DLB). This suggests the amygdala relays alpha-synuclein pathology spread, aiding disease tracking.

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Medical Imaging

Background:

  • Dementia with Lew bodies (DLB) involves widespread neurodegeneration, but its regional drivers are unclear.
  • Alpha-synuclein pathology is hypothesized to spread via structural connections, causing neurodegeneration.
  • This study investigated if connectivity to amygdala and brainstem influences regional brain volume loss.

Purpose of the Study:

  • To determine if brain regions connected to the amygdala and brainstem show greater volume reduction in DLB patients.
  • To assess if overall brain network integration correlates with neurodegeneration in DLB.
  • To explore the role of structural connectivity in the spread of alpha-synuclein pathology.

Main Methods:

  • 80 DLB patients and 65 healthy controls (HCs) underwent T1-weighted and diffusion-weighted MRI.
  • Regional brain volumes were quantified, and white matter tractography built a structural network.
  • Graph theory calculated region distance to amygdala/brainstem and network integration.

Main Results:

  • DLB patients showed reduced brain volumes, particularly in temporal and parietal lobes.
  • Regions more connected to the amygdala exhibited greater volume reductions.
  • No significant correlation was found between distance to the brainstem or network integration and volume reduction.

Conclusions:

  • Structural connectivity with the amygdala predicts regional neurodegeneration in DLB.
  • The amygdala appears to be a key relay for alpha-synuclein pathology spread.
  • Findings support using imaging biomarkers to monitor DLB progression.