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From a neuropathological perspective, usually at a single time\u2010point and often at the end\u2010stage of the disease, it is challenging to understand the cause and effect relationships between these components. There are at least four ways of trying to unravel these relationships. First, genetic studies demonstrate mutations that influence A\u03b2 production, but not tau, can initiate AD; whereas genetic variants influencing AD risk are related to innate immunity and lipid metabolism. Second, studies at early time points show that pathology begins decades before the onset of dementia and indicate different anatomical locations for initiation of A\u03b2 and tau accumulation. Third, cause and effect can be studied in experimental models, but most animal models do not fully replicate AD pathology. However, induced pluripotent stem cells (iPSCs) to study live human neurons has introduced a new perspective. Fourth, clinical trials may alter AD pathology giving insights into cause and effect relationships. Therefore, a sequence of (i) neocortical A\u03b2 accumulation followed by (ii) a microglial inflammatory reaction to A\u03b2, causing neuritic dystrophy which promotes (iii) spread of tau from the limbic system to the neocortex with (iv) progressive tau accumulation and spread resulting in (v) neurodegeneration, explains the evidence. 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