Amyloid plaques (APs) and neurofibrillary tangles (NFTs) are the two diagnostic markers of Alzheimer's disease (AD). The neuropsychological features of AD are closely correlated with the distribution of the NFTs and therefore favor a disease process revolving around neurofibrillary degeneration. The genetics, however, favor a disease process revolving around the APs, principally because mutations in the amyloid precursor protein (A beta PP) are sufficient to cause AD. The inability to reconcile these two aspects of AD has prevented the formulation of a unified theory of pathogenesis. It is interesting to note that all genetic causes and risk factors of AD can increase the physiological burden of neuroplasticity. My hypothesis is that the resultant intensification of the plasticity burden leads to an initially adaptive upregulation of tau phosphorylation and A beta PP turnover, to the subsequent formation of NFTs and APs as independent consequences of excessive plasticity-related cellular activity, and to the eventual loss of neurons, dendrites, and synapses as the ultimate expression of plasticity failure. The two pathological markers of AD are therefore independent manifestations of a more fundamental process through which the many different genotypes of AD trigger an identical clinical and neuropathological phenotype.