Related Experiment Video
Updated: Jun 16, 2026
![PET Imaging of Neuroinflammation Using [11C]DPA-713 in a Mouse Model of Ischemic Stroke](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F57243.jpg&w=3840&q=50)
PET Imaging of Neuroinflammation Using [11C]DPA-713 in a Mouse Model of Ischemic Stroke
Published on: June 14, 2018
Microglia measured by TSPO PET are associated with Alzheimer's disease pathology and mediate key steps in a disease
Samantha M Rossano1, Aubrey S Johnson1, Anna Smith1
1Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, New York, USA.
Introduction:
Evidence suggests microglial activation precedes regional tau and neurodegeneration in Alzheimer's disease (AD). We characterized microglia with translocator protein (TSPO) positron emission tomography (PET) within an AD progression model where global amyloid beta (Aβ) precedes local tau and neurodegeneration, resulting in cognitive impairment.
Methods:
Florbetaben, PBR28, and MK-6240 PET, T1 magnetic resonance imaging, and cognitive measures were performed in 19 cognitively unimpaired older adults and 22 patients with mild cognitive impairment or mild AD to examine associations among microglia activation, Aβ, tau, and cognition, adjusting for neurodegeneration. Mediation analyses evaluated the possible role of microglial activation along the AD progression model.
Results:
Higher PBR28 uptake was associated with higher Aβ, higher tau, and lower MMSE score, independent of neurodegeneration. PBR28 mediated associations between tau in early and middle Braak stages, between tau and neurodegeneration, and between neurodegeneration and cognition.
Discussion:
Microglia are associated with AD pathology and cognition and may mediate relationships between subsequent steps in AD progression.
Insights
Microglial activation, measured by PBR28 PET, is linked to Alzheimer's disease (AD) pathology and cognitive decline. These brain immune cells may play a key role in mediating the progression of AD.
Area of Science:
- Neuroscience
- Radiology
- Immunology
Background:
- Microglial activation is increasingly recognized as an early event in Alzheimer's disease (AD) pathogenesis.
- Understanding the role of microglia in AD progression is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the association between microglial activation and core Alzheimer's disease (AD) pathologies, including amyloid-beta (Aβ) and tau.
- To examine the role of microglial activation in mediating neurodegeneration and cognitive impairment in an AD progression model.
Main Methods:
- Utilized positron emission tomography (PET) with tracers for amyloid-beta (Florbetaben), tau (MK-6240), and translocator protein (TSPO; PBR28).
- Collected T1 magnetic resonance imaging (MRI) and cognitive data (MMSE) from cognitively unimpaired older adults and patients with mild cognitive impairment or mild AD.
- Employed mediation analyses to assess the role of microglial activation in the AD cascade.
Main Results:
- Higher PBR28 uptake (indicating microglial activation) correlated with increased Aβ and tau burden, and lower MMSE scores, irrespective of neurodegeneration.
- PBR28 uptake mediated the relationship between tau pathology (Braak stages), neurodegeneration, and cognitive decline.
Conclusions:
- Microglial activation is significantly associated with AD pathology and cognitive function.
- Microglia may act as a crucial link, mediating the progression from tau accumulation to neurodegeneration and subsequent cognitive impairment in Alzheimer's disease.
