Advances in Alzheimer's disease (AD) research have been challenging and without major breakthroughs in understanding its pathological basis. The reigning hypothesis suggests AD is the result of extracellular amyloid deposition that seed to form amyloid plaques, which then grow and kill neighboring neurons. However, there are several inconsistencies with this hypothesis, not to mention the inability to show clinical benefit in several failed clinical trials by pharmaceuticals (i.e., from Pfizer, Eli Lilly, etc.), and it is in the field's best interest to explore and test multiple hypotheses for pathology rather than drive the majority of research on this single amyloid theory. Reviewing many scientifically peer-reviewed publications, this book describes the "Inside-Out" hypothesis on how amyloid escapes the circulatory system through a dysfunctional blood-brain barrier to bind to the alpha 7 nicotinic acetylcholine receptor on pyramidal neurons. Over time, excessive amounts of amyloid appear to be internalized, resulting in neuron death and lysis. This simple mechanism readily explains plaque composition, size, shape, and location. Based on the current direction of research in the field, this hypothesis appears years from any research and development.
Introduction 1. Alzheimer's Disease Today 2. Seeds of a New Perspective 3. Introducing the "Inside-Out" Hypothesis 4. Addressing Technical Concerns 5. The Good Intentions of Formic Acid 6. Connecting MAP-2 and Cell Lysis 7. Classifying Plaques 8. When is a Star Like a Plaque? 9. The Inflammation Cascade 10. Innocent Ass42 11. The Alpha 7 Nicotinic Acetylcholine Receptor 12. Immunoglobulin: Another Perpetrator 13. Add AD to the List of Autoimmune Diseases 14. The BBB and BRB in AD 15. "Inside-Out" in the Field 16. Alzheimer's Disease Tomorrow Glossary