Alzheimer’s disease: A complex paradigm

Dimitrios Avramopoulos Department of Psychiatry and McKusick Nathans Institute of Genetic Medicine,Johns Hopkins University, Baltimore, Maryland, U.S.A.INTRODUCTIONIn 1901 a 51-year-old woman suffering from progressive mental deterioration came under the care of Dr. Alois Alzheimer while he worked as an attending physician in Frankfurt. A few years later in 1906 Alois Alzheimer gave a remarkable lecture on his patient at the 37th Meeting of the Southwest German Psychiatrists, in which he described for the first time a form of dementia that, subsequently at the suggestion of Emil Kraepelin, became known as Alzheimer’s disease (AD). After the patient’s death and upon microscopic examination of her cerebral cortex Alois Alzheimer found tangled bundles of fibers, which he termed neurofibrillary tangles, and abnormal accumulations of material around the nerves, which he termed senile plaques [for an English translation of the 1907 paper see Alzheimer et al. 1995 (1)]. These findings today still represent the hallmark of AD pathology and are required for the postmortem definite diagnosis of the disease. Unlike the original patient, most individuals affected by AD show initial symptoms at a later age. In the beginning of the twentieth century when AD was first described most people died before theage of 60 and the disorder was an unusual and interesting oddity. Today, with the increase in life expectancy and the dramatic increase of the population of elderly especially in the Western countries, AD represents one of the major health problems of our times. It currently has a prevalence that varies from 5% to 50% for different age groups of people olderthan 65 years (2) and it affects women 1.5 times more often than men (3). In thePART I: GENETICSyear 2000 there were an estimated 4.5 million AD cases in the United States and there will be an expected 13.2 million by 2050 (2). With an average onset in the mid-70s and an average of eight years of gradual deterioration leading to death, AD has a tremendous impact not only on the families of the patients but also on the society and the health care systems. This makes the elucidation of the causes of the disease extremely important and pressing.