Gray matter changes related to microglial activation in Alzheimer's disease
Nicolas Nicastro1, Maura Malpetti2, Elijah Mak3
1Department of Psychiatry, University of Cambridge, Cambridge, UK; Department of Clinical Neurosciences, Geneva University Hospitals, Switzerland.
Abstract:
Neuroinflammation is increasingly recognized as playing a key pathogenetic role in Alzheimer's disease (AD). We examined the relationship between in vivo neuroinflammation and gray matter (GM) changes. Twenty-eight subjects with clinically probable AD (n = 14) and amyloid-positive mild cognitive impairment (n = 14) (age 71.9 ± 8.4 years, 46% female) and 24 healthy controls underwent structural 3T brain MRI. AD/mild cognitive impairment participants exhibited GM atrophy and cortical thinning in AD-related temporoparietal regions (false discovery rate-corrected p < 0.05). Patients also showed increased microglial activation in temporal cortices. Higher 11C-PK11195 binding in these regions was associated with reduced volume and cortical thickness in parietal, occipital, and cingulate areas (false discovery rate p < 0.05). Hippocampal GM atrophy and parahippocampal cortical thinning were related to worse cognition (p < 0.05), but these effects were not mediated by microglial activation. This study demonstrates an association between in vivo microglial activation and markers of GM damage in AD, positioning neuroinflammation as a potential target for immunotherapeutic strategies.
Insights
Neuroinflammation, indicated by microglial activation, is linked to brain gray matter damage in Alzheimer's disease (AD) and mild cognitive impairment. This suggests neuroinflammation is a key factor and potential therapeutic target in AD.
Area of Science:
- Neuroscience
- Radiology
- Immunology
Background:
- Neuroinflammation is increasingly recognized for its role in Alzheimer's disease (AD) pathogenesis.
- Understanding the relationship between in vivo neuroinflammation and brain structural changes is crucial for AD research.
Purpose of the Study:
- To investigate the association between in vivo neuroinflammation and gray matter (GM) changes in individuals with Alzheimer's disease (AD) and mild cognitive impairment (MCI).
- To explore the potential of targeting neuroinflammation for therapeutic strategies in AD.
Main Methods:
- Structural 3T brain MRI was performed on 28 participants with probable AD/amyloid-positive MCI and 24 healthy controls.
- Microglial activation was assessed using 11C-PK11195 positron emission tomography (PET) imaging.
- Gray matter volume and cortical thickness were analyzed in relation to neuroinflammation markers and cognitive function.
Main Results:
- Participants with AD/MCI showed gray matter atrophy and cortical thinning in temporoparietal regions.
- Increased microglial activation was observed in the temporal cortices of AD/MCI patients.
- Higher 11C-PK11195 binding correlated with reduced gray matter volume and cortical thickness in parietal, occipital, and cingulate areas.
- Hippocampal atrophy and parahippocampal thinning were linked to poorer cognition, independent of microglial activation.
Conclusions:
- This study demonstrates a significant association between in vivo microglial activation and gray matter damage in Alzheimer's disease.
- Neuroinflammation emerges as a key pathological feature and a potential therapeutic target for immunotherapeutic strategies in AD.
