Alzheimer's Disease Pathologic Cascades: Who Comes First, What Drives What

This review discusses known and speculated relationships between Alzheimer's disease (AD) biochemical, molecular, and histologic phenomena. In the AD brain, various pathologies including neuritic plaques, neurofibrillary tangles, synaptic loss, oxidative stress, cell cycle re-entry, and mitochondrial changes have all been described. In an attempt to explain what exactly goes wrong in the AD brain various investigators have proposed different heuristic and hierarchical schemes. It is important to accurately define the AD pathology hierarchy because treatments targeting the true apex of its pathologic cascade arguably have the best chance of preventing, mitigating, or even curing this disease.