Seeking a New Paradigm for Alzheimer's Disease: Considering the Roles of Inflammation, Blood-Brain Barrier Dysfunction, and Prion Disease.

There is no effective etiologic treatment for Alzheimer's disease, nor is there a prophylactic medication which delays or prevents its onset. The lack of an accurate paradigm is undoubtedly related to the lack of effective means of prophylaxis and treatment. The current paradigm of beta amyloid in Alzheimer's brains causing cognitive dysfunction must be modified. Despite failed clinical trials, research continues into amyloid-oriented treatments. The persistence of the amyloid hypothesis/paradigm is an example of anchoring and representativeness heuristics described by Kahneman and Tversky in their classic 1974 Science paper. Economic factors also contribute to the persistence of this paradigm. Paradigms impact the scientific process by the following: (1) what is studied; (2) the types of questions that are asked; (3) the structure and nature of the questions; (4) the interpretations of research findings. We review the contribution of inflammation, malfunction of the neurovascular unit, and prion disease to Alzheimer's disease manifestations. Any or all of these are candidates for inclusion into a more accurate, inclusive, and useful new paradigm. By incorporating emerging facts and understanding into a new paradigm, we will enhance our ability to move toward effective prophylaxis and therapy for this tragic disease.