Imaging Microglial Activation During Neuroinflammation and Alzheimer’s Disease

Abstract

Microglial activation is an important pathogenic component of neurodegenerative disease processes. This state of increased inflammation is associated not only with neurotoxic consequences but also neuroprotective effects, e.g., phagocytosis and clearance of amyloid in Alzheimer's disease. In addition, activation of microglia appears to be one of the major mechanisms of amyloid clearance following active or passive immunotherapy. Imaging techniques may provide a minimally invasive tool to elucidate the complexities and dynamics of microglial function and dysfunction in aging and neurodegenerative diseases. Imaging microglia in vivo in live subjects by confocal or two/ multiphoton microscopy offers the advantage of studying these cells over time in their native environment. Imaging microglia in human subjects by positron emission tomography scanning with translocator protein-18 kDa ligands can offer a measure of the inflammatory process and a means of detecting progression of disease and efficacy of therapeutics over time.

Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology

“…Despite the classical hypothesis of the cytotoxic features of activated microglia, recent evidences suggest that microglia are protective in the early stages of AD by promoting amyloid phagocytosis and clearance of fibrillar and soluble amyloid. Microglia can be activated towards a classical proinflammatory phenotype, but also to a neuroprotective phenotype (Venneti et al, 2009). Early microglial activation has been attributed to a neuroprotective role in amyloid pathology, promoting Ab clearance (Yan et al, 2003).…”

Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [18F]-FEPPA

“…Activated microglia thus represent an important marker of neuroinflammation (for a recent review see Venneti et al, 2009). This has been confirmed in a large number of studies that have shown that levels of TSPO and/or microglia are greatly increased in examples of inflammation (as reviewed by Chen and Guilarte, 2008).…”

Imaging microglial activation and glucose consumption in a mouse model of Alzheimer's disease

“…Therefore, the expression of TSPO is a marker of choice to study the extent and role of neuroinflammation in several neurological disorders with the use of radiolabeled TSPO-targeted compounds (Cagnin et al, 2007;Venneti et al, 2009b;Winkeler et al, 2010).…”