ABSTRACT
Epidemiological studies suggest that a variety of factors contribute to the occurrence of Alzheimer’s disease (AD), particularly late-onset AD. Table 2.1 summarizes the most general categories of disease mechanisms that are believed to have a role in the aetiology of AD as well as their presumed order of importance. One ‘risk factor’, such as genetics, may be chosen as primary, and the others may be considered as contributing or permissive.1,2 On the other hand, choosing one risk factor over the others cannot be supported objectively. The least arbitrary assumption is that a variety of factors can contribute to the clinicalpathological syndrome of AD – that is, that AD itself is often a convergence syndrome, particularly in its later-onset forms. In the following discussion, demen-
tia of the Alzheimer’s type is assumed to be a syndrome rather than a single disease with a single, discrete aetiology. A multifactorial model is used in which a variety of environmental and genetic mechanisms can converge to cause the type of scarring of the brain that characterizes the clinical-pathological syndrome of AD. Pathophysiology is discussed under three broad headings: aetiological ‘risk’ factors, molecular neuropathology and brain-behaviour relationships.
