A Brief Introduction to the History of the β-Amyloid Protein (Aβ) of Alzheimer’s Disease

1 Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. Typically, the disease progresses in a prolonged, inexorable manner [1]. Patients initially show symptoms of mild cognitive impairment, which may include some memory loss. As the disease progresses, more severe memory loss occurs (e.g., retrograde amnesia) leading to confusion and lack of orientation. The patient is often institutionalized in this period, as it becomes increasingly difficult for family members to cope with the constant requirements of care. In later stages of the disease, apathy and stupor can occur, and the patient becomes bedridden. The histopathology of AD is characterized by gliosis and tissue atrophy caused by both synaptic and neuronal loss, which are most pronounced in the frontal and temporal cortices [2]. Proteinaceous deposits are seen in both the intracellular and extracellular compartments of the brain, typically in the hippocampus and neocortex. The intracellular deposits consist of neurofibrillary tangles that are made up of paired helical filaments of a hyperphosphorylated form of the cytoskeletal protein tau [3]. Extracellular amyloid plaques are found most commonly in the hippocampus and neocortex and may be diffuse or compact in nature [4]. Amyloid is also deposited as cerebral amyloid angiopathy within smallto medium-sized arterioles [5]. Although neurofibrillary tangles are associated with a number of different types of neurodegenerative disease, the presence of numerous compact or neuritic amyloid plaques is a hallmark feature of Alzheimer’s disease. For this reason, it may be argued that accumulation of the β-amyloid protein (Αβ) is a key step in the pathogenic mechanism of Alzheimer’s disease. In contrast, although the density of neurofibrillary tangles correlates more closely with the cognitive symptoms, it is now commonly thought that tangles are a secondary feature or the underlying disease process [6].