Cited by 138Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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PK11195 labels activated microglia in Alzheimer's disease and in vivo in a mouse model using PET

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Venneti, Sriram, Lopresti, Brian J., Wang, Guoji, Hamilton, Ronald L., Mathis, Chester A., Klunk, William E., Apte, Udayan M., Wiley, Clayton A.·2009·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2007.11.005PMC PMC2745919

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Abstract

Activated microglia may promote neurodegeneration in Alzheimer's disease (AD) and may also help in amyloid clearance in immunization therapies. In vivo imaging of activated microglia using positron emission tomography (PET) could assist in defining the role of activated microglia during AD progression and therapeutics. We hypothesized that PK11195, a ligand that binds activated microglia, could label these cells in postmortem AD tissues and in vivo in an animal model of AD using PET. [(3)H](R)-PK11195 binding was significantly higher in AD frontal cortex compared to controls and correlated mainly with the abundance of immunohistochemically labeled activated microglia. With age, the brains of APP/PS1 transgenic mice showed progressive increase in [(3)H](R)-PK11195 binding and [(11)C](R)-PK11195 retention in vivo assessed using microPET, which correlated with the histopathological abundance of activated microglia. These results suggest that PK11195 binding in AD postmortem tissue and transgenic mice in vivo correlates with the extent of microglial activation and may help define the role of activated microglia in the pathogenesis and treatment of AD.

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Authors: Venneti, S., Lopresti, B. J., Wang, G., Hamilton, R. L., Mathis, C. A., Klunk, W. E., Apte, U. M., & Wiley, C. A.
Affiliations: University of Pittsburgh (US)
Corresponding author: Wiley, Clayton A.
ORCID: Venneti, Sriram
Lopresti, Brian J.
Wang, Guoji
Hamilton, Ronald L.
Mathis, Chester A.
Klunk, William E.
Apte, Udayan M.
Wiley, Clayton A.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2009-08
Volume: 30
Issue: 8
Pages: 1217-1226
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2007.11.005
PMC: PMC2745919
OpenAlex: W2011239875
Cited by: 138
References: 39
Citations by year: 2025: 3 · 2024: 6 · 2023: 3 · 2022: 8 · 2021: 9 · 2020: 11 · 2019: 9 · 2018: 9 · 2017: 11 · 2016: 8 · 2015: 10 · 2014: 13 · 2013: 7 · 2012: 13
FWCI: 3.96
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: University of Pittsburgh
National Institutes of Health
National Institute on Aging (R21AG025829, P50AG005133, R01AG020226, P50 AG05133-21)
National Institute of Mental Health (R01 MH-64921, K24 MH01717, R01MH064921, K24MH001717, R01MH071151)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: PK11195, activated microglia, Alzheimer's disease, positron emission tomography, APP/PS1 mice, microglial activation, amyloid clearance, neurodegeneration, frontal cortex, radioligand binding, in vivo imaging
MeSH terms: Aged, Aged, 80 and over, Aging, Alzheimer Disease, Animals, Astrocytes, Brain, Disease Models, Animal, Female, Frontal Lobe, Humans, Isoquinolines, Male, Mice, Transgenic, Receptors, Cell Surface, Tritium, Amyloid beta-Protein Precursor, Microglia, Disease Progression, Positron-Emission Tomography, Mice, Presenilin-1, Protease Nexins

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PK11195 labels activated microglia in Alzheimer's disease and in vivo in a mouse model using PET

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