Aß Toxicity in Alzheimer’s Disease BT - Molecular Mechanisms of Neurodegenerative Diseases

Abstract

The first diagnosed Alzheimer’s disease patient was Auguste D (Fig. 1), a middle-aged woman cared for by Alsatian clinician-pathologist Alois Alzheimer from 1901 to 1906. Auguste D died in her middle fifties, and Alzheimer, aided by new histochemical methods, found her brain tissue corrupted by an abundance of extracellular and intracellular lesions, the now-familiar plaques and tangles (1). Alzheimer’s research provided the first direct evidence that dementia is the consequence of neurodegenerative mechanisms, not a simple fact of aging. A less diagnostic but equally apt description of the disease also came from Alzheimer’s care of Auguste D. As he tracked his patient’s progressively severe dementia, Alzheimer once asked Auguste D to write her name. She found the task impossible and replied, “I have lost myself” (2). We now know that Alzheimer’s disease (AD) is the most common cause of dementia in older individuals. The number of Alzheimer’s disease patients has grown from the first diagnosed case in 1906 to an estimated 25 million worldwide (3). Complications resulting from AD constitute the fourth leading cause of death in the United States, and the annual cost to the economy exceeds $140 billion (4,5). As the elderly population continues to grow rapidly, AD represents an imminent social as well as medical problem.