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Patterns of Microglial Activation in Early Alzheimer’s Disease

The study covered in this summary was published on as a preprint and has not yet been peer reviewed.

Key Takeaways

  • This study revealed that microglial activation in Alzheimer’s disease (AD) spreads along functional and structural connectivity pathways.

  • A deeper understanding of microglial activation distribution patterns may lead to the development of future anti-inflammatory treatments.

Why This Matters

  • AD clinical presentation is associated with neuroinflammation that spreads along highly connected brain regions.

  • This study supports the important role of microglial activation in neurodegeneration, which may guide future interventional anti-inflammatory therapy to prevent disease progression.

Study Design

  • Thirty-two patients with early AD and 18 age-matched cognitively normal persons who acted as controls were included from the ActiGliA study, a prospective, observational study of the Munich Cluster for Systems Neurology (SyNergy).

    • AD continuum was defined as Clinical Dementia Rating global score ≥0.5, Consortium to Establish a Registry for AD neuropsychological battery score ≤84, and the presence of Aβ pathology on PET and/or CSF examination.

    • Cognitively normal control personss were defined as participants without cognitive impairment who had no indication of Aβ pathology on PET or CSF examination.

  • Translocator protein (TSPO) PET microglial activation, diffusion tensor imaging structural connectivity, and MRI functional connectivity differences were analyzed for the two groups.

  • Associations regarding PET microglial activation with cognitive impairment, dementia severity, and MRI connectivity measures were evaluated between the two groups.

  • Key Results

    • AD participants had increased TSPO PET tracer uptake bilaterally in the parahippocampal region compared to cognitively normal control persons (P < .001).

      • Higher TSPO PET was associated with cognitive impairment and dementia severity in a disease stage–dependent fashion.

    • In AD patients, there was widespread hypoconnectivity between the temporal and cingulate/occipital and frontal regions.

    • Limitations