Novel PET Tracer Detects Brain Astrocyte Reactivity

A choline-based positron emission tomography (PET) tracer can be used to identify brain activity involved in the formation of amyloid plaque in people with cognitive impairment and Alzheimer's disease (AD), according to a new study.

Researchers at Imperial College London (Imperial; United Kingdom), Cardiff University (United Kingdom), and other institutions enrolled 11 older, cognitively impaired subjects and nine age-matched healthy controls in a study of the viability of 11C-BU99008, a new PET tracer, to selectively image astrocyte reactivity, which may precede early pathological signs of AD, such as the formation of β-amyloid plaque and tau tangles. The patients also underwent 3T magnetic resonance imaging (MRI) and 18F-florbetaben PET imaging to identify β-amyloid plaque.

The results showed that 11C-BU99008 uptake was higher in eight β-amyloid-positive patients with cognitive impairment across the whole brain, but particularly in frontal, temporal, medial temporal, and occipital lobes, compared with the control group. Biological parametric mapping demonstrated a positive voxel-wise neuroanatomical correlation between 11C-BU99008 and 18F-florbetaben uptake, confirming that 11C-BU99008 could measure astrocyte reactivity. The study was published on July 15, 2021, in Molecular Psychiatry.

“This proof-of-concept study provides direct evidence that 11C-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer's disease,” concluded senior author Paul Edison, PhD, of the Imperial department of brain sciences, and colleagues. “Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high β-amyloid load.”

Astrocytes have a wide range of roles in the central nervous system, and astrocyte reactivity can increase the expression of inflammatory mediators, reactive oxygen species (ROS), and β-amyloid deposition. In fact, it has been suggested that astrocyte reactivity may be a tissue response to β-amyloid and may have a protective role by phagocytosing and degrading it. Minimally invasive methods for monitoring astrocyte reactivity in patients with late-life cognitive impairment can provide a tool for testing their contributions to disease progression.

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Cardiff University