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

被引：100

作者：

Venneti, Sriram ^{[1
]}

Lopresti, Brian J. ^{[2
]}

Wang, Guoji ^{[1
]}

Hamilton, Ronald L. ^{[1
]}

Mathis, Chester A. ^{[2
]}

Klunk, William E. ^{[3
]}

Apte, Udayan M. ^{[1
]}

Wiley, Clayton A. ^{[1
]}

机构：

[1] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15213 USA

[3] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA

来源：

NEUROBIOLOGY OF AGING | 2009年 / 30卷 / 08期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; Microglia; PET; PK11195; Peripheral benzodiazepine receptor; Astrocyte; PERIPHERAL BENZODIAZEPINE-RECEPTORS; AMYLOID-BETA-PEPTIDE; TRANSGENIC MODELS; BINDING-SITES; BRAIN; PATHOLOGY; IMMUNIZATION; DEPOSITION; NEUROPATHOLOGY; ENCEPHALITIS;

D O I：

10.1016/j.neurobiolaging.2007.11.005

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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. [H-3](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 [H-3](R)-PK11195 binding and [C-11](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. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：1217 / 1226

页数：10

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