Alzheimer's disease (AD) is an age-related, neurodegenerative disorder that represents the most common cause of dementia and is one of the leading causes of medical morbidity and mortality in the developed world. The implications of increasing longevity and shifting population demographics have led to the recognition of AD as a public health problem of major proportions. The percentage of the US population over age 65 will more than double over the next 30 to 40 years. According to these projections, as many as 10 million persons will be afflicted with dementia, the majority of whom will suffer from AD, with associated annual health care costs of over $100 billion (Cummings, 1995). On a personal level, the insidious but relentless decline in the affected individual's cognitive and functional abilities imposes a particularly heavy burden on patient, caregivers and family members alike. These considerations have greatly increased public awareness of AD during the past 20 years, and have stimulated the increasingly rapid pace of scientific progress directed toward the development of effective, disease-modifying treatments.
In 1907, Alois Alzheimer published the initial report of the clinical and pathologic features of the disease that was soon named after him by Emil Kraepelin (Alzheimer, 1907; Kraepelin, 1910; Maurer et al., 1997). This report summarized a lecture he had given the prior year on the case of ‘Auguste D’, a 51-year-old woman admitted in 1901 to the Hospital for the Mentally Ill and Epileptics in Frankfurt, Germany. Alzheimer described a syndrome of ‘rapidly increasing memory impairments’, aphasia, disorientation, paranoia, and auditory hallucinations. His detailed histopathological analysis upon her death in 1906, which was aided by the new staining techniques introduced by his colleague Franz Nissl, revealed ‘numerous small miliary foci … caused by the deposition of a peculiar substance in the cortex’. These ‘foci’ or neuritic plaques, as they came to be called, were accompanied by extensive loss of cortical neurons and striking neurofibrillary changes: ‘In the center of an otherwise normal cell there stand out one or several fibrils due to their characteristic thickness and peculiar impregnability.’ Alzheimer provided a more thorough description of this original case, along with an account of a second case (‘Johann F’.) from his Munich clinic, in a subsequent publication that included numerous illustrations of the characteristic neuritic plaques and neurofibrillary tangles (Alzheimer, 1911).