Alzheimer Disease: Advances in Pathogenesis, Diagnosis, and Therapy

Abstract

Alzheimer disease (AD)9, the most frequent cause of dementia in Western societies, affects approximately 5.5 million people in the US and more than 35 million people worldwide. Common symptoms of this disease include memory loss, confusion, irritability, and aggression. Normal bodily functions are progressively lost, with AD becoming fatal within 3 to 9 years after diagnosis. The major risk factor for AD is advanced age. After the age of 65 years, the incidence of AD doubles every 5 years. As the size of the elderly population increases, particularly the “baby boomers,” the prevalence will approach 30 to 60 million cases in the US alone by 2050. The pathogenesis of AD is not clear, but the major pathogenetic mechanisms that have been suggested include the accumulation of misfolded proteins in the aging brain, which causes oxidative and inflammatory damage, which in turn leads to energy failure and synaptic dysfunction. A very small proportion (<1%) of AD cases are familial with early onset, and such cases have been linked to mutations in genes encoding amyloid precursor protein (APP) and presenilins 1 and 2. There is also a strong genetic association between one variant of apolipoprotein E (apo E) and the risk for developing AD. Over the last 10 years, there has been increased interest in understanding the pathogenesis of this disease and in the development of new therapies. We interview 4 specialists and examine the latest advances in pathogenesis, diagnosis, and therapy for this debilitating disease. Can you summarize briefly some new insights into the pathogenesis of AD? JoAnne McLaurin: We have understood for years that the biggest risk factor for AD is aging. We are now starting to unravel the effects of aging on memory function and link this back to disease progression. New data have arisen that link …