β and p-tau have been proven to predict disease progression independently in various investigations. Both proteinopathies, according to a hypothesised framework, synergistically enhance downstream neurodegeneration. The presence of such a synergism would imply that the combined effect of A β and p-tau on AD progression is greater than the sum of their individual effects at the same level. Indeed, recent studies demonstrate that rather than neurodegeneration, the synergistic interaction between brain A and p-tau drives AD-related metabolic decline in a cognitively normal population. In the adult human brain, billions of synapses join more than a hundred billion long branching extensions of neurons to build complex chemical connections between inter-neuron circuits. Nonlinear cumulative effects of two active chemicals with similar or related consequences of their distinct activities, or active compounds with sequential or complementary activities, are known as synergistic effects.