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.‎ * The clear‎,‎ compelling‎,‎ and unifying ‎"‎Inside‎-Out‎"‎ hypothesis of AD is brought to life through a string of scientific publications‎,‎ synthesizing many known features of disease pathology* A high‎-level text on AD pathology‎,‎ and suggestions for progress in a stagnating field* Point‎-by‎-point discussion on the issues surrounding the current amyloid cascade‎,‎ and possible reasons why current clinical trials have failed* Contains high‎-quality photomicrographs in support of the ‎"‎Inside‎-Out‎"‎ hypothesis using single‎,‎ double‎,‎ and triple immunohistochemistry on human AD CNS tissues* Chapters address the need for a unifying plaque nomenclature‎,‎ the importance of intracellular amyloid‎,‎ the blood‎-brain barrier‎,‎ inflammation‎,‎ and autoimmunity