Connections, Cognition and Alzheimer’s Disease

Alzheimer's disease invades the brain from the inside. Unlike an abcess, a metas­ tasis or an infarct, the disease follows specific tracks and avoids certain cortical areas while flourishing in others. Any observer is struck by the exquisite selectiv­ ity of the lesions and could, indeed, conclude that Alzheimer's disease knows neuroanatomy. However, should the term "disease" be used to define this disor­ der? Several genes, located on at least three different chromosomes, have been implicated in the disease. The ApoE4 genotype has been shown to be an impor­ tant risk factor, but dementia pugilistica also suggests that environment can be involved in at least some aspects of the disorder. These data favor the now preva­ lent view that Alzheimer's disease should instead be considered as a syndrome, and probably all of the contributors to this volume are ready to endorse this point of view. If "Alzheimer's syndrome" is the final common pathway to several pathoge­ netic mechanisms, there should be an event at one point in the course of the spe­ cific etiology that triggers a somewhat stereotypic diffusion process along some neural connections. Scientists who are fascinated by the way in which the ner­ vous system has morphologically encoded its function after a long phylogenetic history are also fascinated by this pathological progression of Alzheimer's syn­ drome.