Targeting neuroinflammation in Alzheimer’s disease: evidence for NSAIDs and novel therapeutics

ABSTRACT

Introduction: There is an increasing recognition of the immune system as an important mediator in the pathogenesis of Alzheimer’s disease (AD). As immune system modulators, non-steroidal anti-inflammatory drugs (NSAIDs) garnered initial enthusiasm from pre-clinical and epidemiologic studies as agents to reduce the risk of AD.

Areas covered: This article will examine the evidence for the use of NSAIDs in AD by discussing the proposed mechanism of action, results from epidemiologic studies, and data from randomized controlled trials. In addition, a survey of several novel approaches to targeting inflammatory pathways currently in pre-clinical and clinical phases of development is presented. These agents primarily act to modulate microglial functioning, enhance amyloid-β phagocytosis, suppress potentially harmful pro-inflammatory responses, or enhance systemic immunity.

Expert commentary: While long-term use of NSAIDs is associated with a reduced incidence of AD in epidemiologic studies, randomized controlled trials have not replicated these findings. Thus, NSAID use cannot currently be recommended either for primary prevention or treatment of AD. However, the available evidence does suggest that cognitively normal patients taking long-term courses of NSAIDs for other indications likely have a decreased risk of AD, which represents an important finding given the high prevalence of NSAID use among older adults.

KEYWORDS:

• Alzheimer disease
• anti-inflammatory agents
• inflammation
• immune system
• neuroinflammation
• non-steroidal anti-inflammatory drug (NSAID)

Declaration of interest

G.T Grossberg serves as a consultant/speaker for Accera, Actavis, Avanir, Baxter, Daiichi Sankyo, Forest, GE Pharmaceuticals, Genentech, Lundbeck, Novartis, Otsuka, Roche, and Takeda. G.T. Grossberg’s department has received research support from Accera, Baxter, Forest, Janssen, Novartis, and Noven. G.T. Grossberg serves on safety monitoring boards for EryDel, Merck, and Newron. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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