Amyloid beta and Alzheimer disease therapeutics: the devil may be in the details

Abstract

Alzheimer disease (AD) is characterized by the progressive accumulation of amyloid beta protein (Abeta) in areas of the brain serving cognitive functions such as memory and language. The first of two separate reports (see the related articles beginning on pages 415 and 440) reveals that intrinsic T cell reactivity to the self-antigen Abeta exists in many humans and increases with age. This finding has implications for the design of Abeta vaccines. The second report demonstrates that a number of FDA- approved nonsteroidal anti-inflammatory drugs are capable of lowering Abeta levels in mice. The work suggests that further testing of the therapeutic utility of these types of compounds for the potential treatment of AD is warranted.

Figure 1

Model of how certain NSAIDs decrease Aβ42 production. NSAIDs may directly bind to the γ-secretase complex and alter APP processing to decrease Aβ42 production and also change production of other Aβ species.