A Theoretical Analysis of the Synergy of Amyloid and Tau in Alzheimer's Disease

Amyloid plaques and Tau protein neurofibrillary tangles are considered the two most important pathogenic factors in Alzheimer's disease. The prevailing amyloid cascade hypothesis suggests that amyloid-beta (A beta) elevation induces downstream Tau hyperphosphorylation and aggregation, synaptic dysfunction, and neuronal loss that ultimately results in cognitive impairment. Alternatively, the dual-pathway hypothesis suggests that A beta and abnormal Tau are two independent factors that exert synergistic effects on synaptic dysfunction and neuronal loss. We hypothesize that the intrinsic interaction of A beta and Tau would better predict cognitive impairment. Herein, we propose an A beta-Tau interactive model based on a review of the medical literature, mathematic modeling, and analysis of our clinicopathological data.