Imaging microglial activation and amyloid burden in amnestic mild cognitive impairment
Dunja Knezevic1,2, Nicolaas Paul Lg Verhoeff1,3, Sina Hafizi1
11 University of Toronto, Toronto, Ontario, Canada.
Abstract:
Amnestic mild cognitive impairment (aMCI) is defined as a transitional state between normal aging and Alzheimer's disease (AD). Given the replicated finding of increased microglial activation in AD, we sought to investigate whether microglial activation is also elevated in aMCI and whether it is related to amyloid beta (Aβ) burden in-vivo . Eleven aMCI participants and 14 healthy volunteers completed positron emission tomography (PET) scans with [18F]-FEPPA and [11C]-PIB. Given the known sensitivity in affinity of second-generation TSPO radioligands, participants were genotyped for the TSPO polymorphism and only high-affinity binders were included. Dynamic [18F]-FEPPA PET images were analyzed using the 2-tissue compartment model with arterial plasma input function. Additionally, a supplementary method, the standardized uptake value ratio (SUVR), was explored. [11C]-PIB PET images were analyzed using the Logan graphical method. aMCI participants had significantly higher [11C]-PIB binding in the cortical regions. No significant differences in [18F]-FEPPA binding were observed between aMCI participants and healthy volunteers. In the aMCI group, [18F]-FEPPA and [11C]-PIB bindings were correlated in the hippocampus. There were no correlations between our PET measures and cognition. Our findings demonstrate that while Aβ burden is evident in the aMCI stage, microglial activation may not be present.
Insights
Amyloid beta burden is present in early Alzheimer's transition (aMCI), but microglial activation is not detected in this stage. This study used PET scans to compare aMCI patients and healthy volunteers.
Area of Science:
- Neuroscience
- Radiology
- Gerontology
Background:
- Amnestic mild cognitive impairment (aMCI) represents a preclinical stage between normal aging and Alzheimer's disease (AD).
- Microglial activation is a known hallmark of AD, but its presence in the earlier aMCI stage is uncertain.
- Investigating microglial activation and amyloid-beta (Aβ) burden in aMCI is crucial for understanding disease progression.
Purpose of the Study:
- To determine if microglial activation is elevated in aMCI compared to healthy controls.
- To investigate the relationship between in-vivo Aβ burden and microglial activation in aMCI.
- To explore potential correlations between these biomarkers and cognitive function.
Main Methods:
- Positron emission tomography (PET) scans using [18F]-FEPPA (for microglial activation) and [11C]-PIB (for Aβ burden) were performed on 11 aMCI participants and 14 healthy volunteers.
- Participants were genotyped for the TSPO polymorphism, and only high-affinity binders were included.
- PET data were analyzed using kinetic modeling (2-tissue compartment model for [18F]-FEPPA) and graphical methods (Logan analysis for [11C]-PIB).
Main Results:
- aMCI participants showed significantly higher cortical [11C]-PIB binding, indicating increased Aβ burden.
- No significant differences in [18F]-FEPPA binding were found between aMCI and healthy groups, suggesting no elevated microglial activation.
- A correlation was observed between [18F]-FEPPA and [11C]-PIB binding in the hippocampus within the aMCI group.
Conclusions:
- Aβ deposition is detectable in the aMCI stage.
- Elevated microglial activation may not be a characteristic feature of aMCI.
- The findings suggest a dissociation between Aβ accumulation and neuroinflammation in the early stages of cognitive decline.
