As the societal and economic burdens of Alzheimer's disease (AD) continue to mount, so does the need for therapies that slow the progression of the illness. Beta amyloid has long been recognized as the pathologic hallmark of AD, and the past decade has seen significant progress in the development of various immunotherapeutic approaches targeting beta amyloid. This paper reviews active and passive approaches aimed at beta amyloid, with a focus on clinical trial data. 1. Introduction Alzheimer’s disease (AD) is by far the most common form of dementia, and the social and economic burdens of AD continue to mount. In 2010, an estimated 36 million people worldwide were living with dementia—a number that is projected to increase to 66 million in 2030, and 115 million in 2050 [1]. According to the World Alzheimer Report, the worldwide cost of dementia is estimated at USD $604 billion for 2010 [1], and according to one model, this cost has increased by 34% between 2005 and 2009 [2]. These statistics must be considered in parallel with the immeasurable emotional and psychological burdens that AD places on patients and families. Significant progress in the treatment of AD has been made since the initial description of the disease by Alois Alzheimer in 1907 [3]. Cholinesterase inhibitors and memantine are potential therapies for the management of many cognitive symptoms of AD, but these neurotransmitter-based approaches do not address the underlying pathology of the illness, and ultimately fail to prevent its progression. The pathologic triad of AD—the accumulation of toxic beta amyloid with the formation of extracellular beta-amyloid-containing plaques, the development of intracellular neurofibrillary tangles, and the degeneration of cerebral neurons—provides numerous potential targets for disease-modifying therapies. Multiple lines of evidence now suggest, however, that it is the production and/or deposition of toxic forms of beta amyloid, along with the slowing of beta-amyloid clearance, that act as the central and primary events in AD pathogenesis, while neurofibrillary tangle formation and neuronal cell death occur downstream in this amyloid cascade [4–6]. Recent in vitro work has demonstrated that beta-amyloid dimers (the major form of soluble oligomers in the human brain) isolated from patients with AD induce both the abnormal phosphorylation of tau that is characteristic of AD and the degeneration of neurites, providing further confirmation of the pivotal role of beta amyloid in the pathogenesis of AD [7]. The search for a disease modifying therapy—one that
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