title: Tracking neuroinflammation in Alzheimer's disease: the role of positron emission tomography imaging.
abstract: Alzheimer's disease (AD) has been reconceptualized as a dynamic pathophysiological process, where the accumulation of amyloid-beta (Aβ) is thought to trigger a cascade of neurodegenerative events resulting in cognitive impairment and, eventually, dementia. In addition to Aβ pathology, various lines of research have implicated neuroinflammation as an important participant in AD pathophysiology. Currently, neuroinflammation can be measured in vivo using positron emission tomography (PET) with ligands targeting diverse biological processes such as microglial activation, reactive astrocytes and phospholipase A2 activity. In terms of therapeutic strategies, despite a strong rationale and epidemiological studies suggesting that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the prevalence of AD, clinical trials conducted to date have proven inconclusive. In this respect, it has been hypothesized that NSAIDs may only prove protective if administered early on in the disease course, prior to the accumulation of significant AD pathology. In order to test various hypotheses pertaining to the exact role of neuroinflammation in AD, studies in asymptomatic carriers of mutations deterministic for early-onset familial AD may prove of use. In this respect, PET ligands for neuroinflammation may act as surrogate markers of disease progression, allowing for the development of more integrative models of AD, as well as for the measuring of target engagement in the context of clinical trials using NSAIDs. In this review, we address the biological basis of neuroinflammatory changes in AD, underscore therapeutic strategies using anti-inflammatory compounds, and shed light on the possibility of tracking neuroinflammation in vivo using PET imaging ligands.
authors.forename: Eduardo Rigon
authors.initials: ER
authors.lastname: Zimmer
authors.forename: Antoine
authors.initials: A
authors.lastname: Leuzy
authors.forename: Andréa Lessa
authors.initials: AL
authors.lastname: Benedet
authors.forename: John
authors.initials: J
authors.lastname: Breitner
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.affiliation: Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging (MCSA), Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada. pedro.rosa@mcgill.ca.
authors.forename: Pedro
authors.initials: P
authors.lastname: Rosa-Neto
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D004660:Encephalitis / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D049268:Positron-Emission Tomography
chemical_list: D000893:Anti-Inflammatory Agents