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Abstract
In Alzheimer's disease (AD), persistent microglial activation as sign of chronic neuroinflammation contributes to disease progression. Our study aimed to in vivo visualize and quantify microglial activation in 13- to 15-month-old AD mice using [11C]-(R)-PK11195 and positron emission tomography (PET). We attempted to modulate neuroinflammation by subjecting the animals to an anti-inflammatory treatment with pioglitazone (5-weeks' treatment, 5-week wash-out period). [11C]-(R)-PK11195 distribution volume values in AD mice were significantly higher compared with control mice after the wash-out period at 15 months, which was supported by immunohistochemistry data. However, [11C]-(R)-PK11195 μPET could not demonstrate genotype- or treatment-dependent differences in the 13- to 14-month-old animals, suggesting that microglial activation in AD mice at this age and disease stage is too mild to be detected by this imaging method.
Highlights
In Alzheimers disease (AD), activated microglia are found in the direct vicinity of amyloid β (Aβ) plaques
At 15 months, a significantly higher distribution volume (DV) could be observed in the whole brain (WB), CX, HC and CB of Tg mice, this significance disappeared after posthoc Bonferroni correction for multiple comparisons
Together with the current study, these data may indicate that at earlier Alzheimer’s disease stages, the number of activated microglia is below the limit of detection by [11C]-(R)-PK11195 μPET
Summary
In AD, activated microglia are found in the direct vicinity of amyloid β (Aβ) plaques. They take on a neuroprotective role, but with disease progression, secretion of neurotoxic proinflammatory molecules results in a chronic neuroinflammatory stage and neurodegeneration (Perry et al, 2010). [11C]-(R)-PK11195 has been used in animal and human positron emission tomography (PET) studies to image the dynamics of activated microglia in neurological disorders including AD (Venneti et al, 2009). We evaluated the consumption of [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and the effect of pioglitazone, an agonist for the nuclear peroxisome proliferator-activated receptor γ (PPAR-γ), as compound with microglia-modulating properties (Kummer and Heneka, 2008)
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