Dataset Information

Clinical PET Imaging of Microglial Activation: Implications for Microglial Therapeutics in Alzheimer's Disease.

ABSTRACT: In addition to extracellular ?-amyloid plaques and intracellular neurofibrillary tangles, neuroinflammation has been identified as a key pathological characteristic of Alzheimer's disease (AD). Once activated, neuroinflammatory cells called microglia acquire different activation phenotypes. At the early stage of AD, activated microglia are mainly dominated by the neuroprotective and anti-inflammatory M2 phenotype. Conversely, in the later stage of AD, the excessive activation of microglia is considered detrimental and pro-inflammatory, turning into the M1 phenotype. Therapeutic strategies targeting the modulation of microglia may regulate their specific phenotype. Fortunately, with the rapid development of in vivo imaging methodologies, visualization of microglial activation has been well-explored. In this review, we summarize the critical role of activated microglia during the pathogenesis of AD and current studies concerning imaging of microglial activation in AD patients. We explore the possibilities for identifying activated microglial phenotypes with imaging techniques and highlight promising therapies that regulate the microglial phenotype in AD mice.

SUBMITTER: Shen Z

PROVIDER: S-EPMC6186779 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Clinical PET Imaging of Microglial Activation: Implications for Microglial Therapeutics in Alzheimer's Disease.

Shen Zhiwei Z Bao Xinjie X Wang Renzhi R

Frontiers in aging neuroscience 20181008

In addition to extracellular β-amyloid plaques and intracellular neurofibrillary tangles, neuroinflammation has been identified as a key pathological characteristic of Alzheimer's disease (AD). Once activated, neuroinflammatory cells called microglia acquire different activation phenotypes. At the early stage of AD, activated microglia are mainly dominated by the neuroprotective and anti-inflammatory M2 phenotype. Conversely, in the later stage of AD, the excessive activation of microglia is con ...[more]

PMID: 30349474

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Project description:BackgroundMetabotropic glutamate subtype 5 receptors (mGluR5) modulate synaptic transmission and may constitute an important therapeutic target in Alzheimer's disease (AD) by mediating the synaptotoxic action of amyloid-β oligomers. We utilized the positron emission tomography (PET) radioligand [18F]FPEB to investigate mGluR5 binding in early AD.MethodsSixteen individuals with amnestic mild cognitive impairment (MCI) due to AD or mild AD dementia who were positive for brain amyloid were compared to 15 cognitively normal (CN) participants who were negative for brain amyloid. Diagnostic groups were well balanced for age, sex, and education. Dynamic PET scans were acquired for 60 min, starting at 60 min after the initial administration of up to 185 MBq of [18F]FPEB using a bolus-plus-constant-infusion method (Kbol = 190 min). Equilibrium modeling with a cerebellum reference region was used to estimate [18F]FPEB binding (BPND) to mGluR5. Analyses were performed with and without corrections for gray matter atrophy and partial volume effects.ResultsLinear mixed model analysis demonstrated a significant effect of group (p = 0.011) and the group × region interaction (p = 0.0049) on BPND. Post hoc comparisons revealed a significant reduction (43%) in mGluR5 binding in the hippocampus of AD (BPND = 0.76 ± 0.41) compared to CN (BPND = 1.34 ± 0.58, p = 0.003, unpaired t test) participants, and a nonsignificant trend for a reduction in a composite association cortical region in AD (BPND = 1.57 ± 0.25) compared to CN (BPND = 1.86 ± 0.63, p = 0.093) participants. Exploratory analyses suggested additional mGluR5 reductions in the entorhinal cortex and parahippocampal gyrus in the AD group. In the overall sample, hippocampal mGluR5 binding was associated with episodic memory scores and global function.Conclusions[18F]FPEB-PET revealed reductions in hippocampal mGluR5 binding in early AD. Quantification of mGluR5 binding in AD may expand our understanding of AD pathogenesis and accelerate the development of novel biomarkers and treatments.

Dataset Information

Clinical PET Imaging of Microglial Activation: Implications for Microglial Therapeutics in Alzheimer's Disease.

Publications

Clinical PET Imaging of Microglial Activation: Implications for Microglial Therapeutics in Alzheimer's Disease.

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