APOE and early-onset autosomal dominant Alzheimer disease: By analogy, in Alzheimer's disease, there is a fundamental, age-associated imbalance between the dynamically opposed physiological processes that mediate plasticity, i.e. between “synaptoblastic” and “synaptoclastic” activity, physiological mediators of synaptic development, maintenance, repair and remodelling, signaled via APP, its derivative peptides, ApoE and tau and modulated by all of the many disparate factors associated with Alzheimer's disease.