Abstract: Although many causes of Alzheimer’s disease (AD) may exist, both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β (Aβ) and tau protein is the central event causing the pathology. However, that conclusion could be only partly true, and there is conflicting evidence about the role of both proteins in AD, being able to precede and influence one another. Some researchers argue that these proteins are mere executors rather than primary causes of pathology. Therefore, there have been continuing refinements of both hypotheses, with alternative explanations proposed. Aβ and tau proteins may be independently involved in specific neurotoxic pathways; yet there may be other crucial processes going on in early AD. Moreover, accumulating evidence suggests that Aβ and tau act synergistically, rather than additively in disease onset (Jeremic et al., 2021, 2023a).