Patterns of Microglial Activation in Early Alzheimer’s Disease

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.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

• The small sample size restricted the statistical power of some of the analyses.

  • The presented data should be confirmed in independent datasets.

• The authors relied on biomarker-based stratification and in-depth phenotyping.

  • Pathologic verification was unavailable to confirm the clinical diagnoses.

  • The passing of [¹⁸F]GE-180 across the blood-brain barrier to access microglial activation is limited

  Disclosures

  • Funding was provided by the German Center for Neurodegenerative Disorders, the Hirnliga e. V., and the Deutsche Forschungsgemeinschaft.

  • The authors have disclosed no relevant financial relationships.

  This is a summary of a preprint research study, MRI Connectivity-Based Spread of Microglial Activation in Early Alzheimer’s Disease,” written by Boris-Stephan Rauchmann, MD from the University Hospital, LMU Munich and colleagues on MedRxiv.org and is provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.

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