ABSTRACT
The traditional view that any disease has one cause, mechanism and phenotype fits uncomfortably with contemporary knowledge concerning many of the common neurological disorders. Not only do these complex traits arise from the interplay of several susceptibility genes but, in many instances, the disease process must also be triggered by (mostly as yet unidentified) environmental factors. Furthermore, within the context of a specific condition, tissue injury may involve a cascade of interacting but specifically different events; and, conversely, an identical set of pathological processes may be expressed as entirely different clinical phenotypes. In short, these disorders are characterized by complexity and heterogeneity, but these terms convey different meanings. Complexity defines interrelated events which are nevertheless part of the same core process. Heterogeneity implies a specifically different sequence of events, determined by variations in the interplay of aetiological factors and expressed as shared or distinct phenotypes. Alternatively, genetic or environmental conditions may modify a core process to produce both complexity and/or heterogeneity. These principles are well illustrated by reference to neurodegenerative disorders characterized by impaired memory.
