ABSTRACT
One of the most long-standing debates in Alzheimer’s disease (AD) research concerns the relative importance, or the relative temporal relationships, of βamyloid plaques and abnormally phosphorylated tau proteins, both of which are seen as histopathologic hallmarks of the disease. At present the pendulum has swung towards amyloid being the main protagonist. The amyloid cascade hypothesis states that overproduction, decreased clearance, or enhanced aggregation of the amyloid β-42 protein (Aβ42) derived from an abnormal cleavage of the transmembranous amyloid precursor protein (APP) results in a cascade of events, culminating in cell death and dementia (Figure 5.1). A number of strategies are being explored as ways of preventing the oligomerization and aggregation of Aβ42 or of increasing its removal from the CNS.
