Toward a comprehensive theory of Alzheimer's disease--challenges, caveats, and parameters

The task of developing a unifying theory of Alzheimer's disease faces several impediments. The most difficult include: the impact of scientific orthodoxy on the acceptance of new ideas; the uncertain relationship between aging and disease(s); the long time course of the degenerative process; the heterogeneity in the genotype and phenotype of the disease; the complex interactions among genetic and other risk factors (many of which are not yet known); the poorly understood nonlinear relationships between the neurobiological and the clinical phenotypes of the disease--namely, viewing clinical symptoms as emergent behavior(s) of a complex system; and the paucity of appropriate models or modeling systems for human disease(s) such as Alzheimer's.