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Updated: Jan 4, 2026
Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
Published on: June 1, 2016
Microglial activation, but not tau pathology, is independently associated with amyloid positivity and memory
James Zou1, Sha Tao2, Aubrey Johnson1
1Taub Institute, Columbia University Irving Medical Center, New York, NY, USA.
Abstract:
We sought to determine if upstream amyloid accumulation and downstream cognitive impairment have independent relationships with microglial activation and tau pathology. Fifty-eight older adults were stratified by amyloid and cognitive status based on 18F-florbetaben PET, history, and neuropsychological testing. Of these, 57 had 11C-PBR28 PET to measure microglial activation and 43 had 18F-MK-6240 PET to measure tau pathology. Amyloid and cognitive status were associated with increased overall binding for both 11C-PBR28 and 18F-MK-6240 (p's < 0.01). While there was no interaction between amyloid and cognitive status in their association with 11C-PBR28 binding (p = 0.6722), there was an interaction in their association with 18F-MK-6240 binding (p = 0.0115). Binding of both radioligands was greater in amyloid-positive controls than in amyloid-negative controls; however, this difference was seen in neocortical regions for 11C-PBR28 and only in medial temporal cortex for 18F-MK-6240. We conclude that, in the absence of cognitive symptoms, amyloid deposition has a greater association with microglial activation than with tau pathology.
Insights
Amyloid accumulation is linked to microglial activation and tau pathology in older adults. In cognitively unimpaired individuals, amyloid positively correlates more with microglial activation than tau pathology.
Area of Science:
- Neuroscience
- Neuropathology
- Radiochemistry
Background:
- Amyloid-beta plaques and tau tangles are key hallmarks of Alzheimer's disease.
- Microglial activation is an early inflammatory response in neurodegenerative diseases.
- Understanding the interplay between amyloid, tau, and neuroinflammation is crucial for early diagnosis and treatment.
Purpose of the Study:
- To investigate the independent relationships between amyloid accumulation, cognitive status, microglial activation, and tau pathology.
- To determine if amyloid and cognitive impairment have distinct associations with neuroinflammation and tau burden.
- To explore the regional differences in these associations.
Main Methods:
- Utilized positron emission tomography (PET) with radioligands targeting amyloid (18F-florbetaben), microglial activation (11C-PBR28), and tau pathology (18F-MK-6240).
- Stratified 58 older adults based on amyloid PET status and cognitive function (neuropsychological testing and clinical history).
- Analyzed the association between amyloid/cognitive status and PET-derived binding of 11C-PBR28 and 18F-MK-6240.
Main Results:
- Both amyloid positivity and cognitive impairment were associated with increased microglial activation and tau pathology.
- Amyloid positivity showed a stronger association with microglial activation in neocortical regions compared to tau pathology.
- An interaction between amyloid and cognitive status was observed for tau pathology but not for microglial activation.
Conclusions:
- Amyloid deposition is associated with both microglial activation and tau pathology.
- In cognitively unimpaired individuals, amyloid accumulation is more closely linked to microglial activation than to tau pathology.
- These findings highlight the differential roles of amyloid in initiating neuroinflammation and subsequent tau spread.
