Targeting microglia for the treatment of Alzheimer’s disease

Abstract

Introduction: Activated microglia are associated with the progression of Alzheimer’s disease (AD), as well as many other neurodegenerative diseases of aging. Microglia are therefore key targets for therapeutic intervention.

Areas covered: β-amyloid (Aβ) deposits activate the complement system, which, in turn, stimulates microglia to release neurotoxic materials. Research has focused primarily on anti-inflammatory agents to temper this toxic effect. More recently there has been a focus on converting microglia from this M1 state to an M2 state in which the toxic effects are reduced and their phagocytic activity toward Aβ enhanced. Studies in transgenic mice have suggested a number of possible anti-inflammatory approaches but they may not always be a good model. An example is vaccination with antibodies to Aβ, which is effective in mouse models, but has repeatedly failed in clinical trials. Biomarker studies indicate that AD commences many years prior to clinical onset.

Expert opinion: A hopeful approach to a disease-modifying treatment of AD is to administer agents that inhibit the inflammatory stimulation of microglia or successfully convert them to an M2 state. However, any such treatment must be started early in the disease.

Keywords:

• β-amyloid protein
• complement
• IL-1
• IL-6
• inflammation
• membrane attack complex
• phagocytosis

Declaration of interest

The authors are significant shareholders in Aurin Biotechnology, Inc., which is developing ATAC as a treatment for AD and many diseases where complement over activity contributes to the pathology. 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.

Notes

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