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Abnormalities in tau modification and tau aggregation are a characteristic histopathological hallmark of Alzheimer's disease (AD). However it is less clear, how tau pathology is linked to other factors, e.g. the formation of amyloid plaques, mutations in the presenilin gene, or the ApoE genotype that all have been shown to contribute to the disease. In this article, data reporting tau's interactions with other factors that may be relevant for AD and that have been obtained from various types of in vitro experiments, cell culture experiments and animal models are summarized and brought into a mechanistic framework. Evidences for functional links of these interactions to neurodegenerative events characteristic for AD are discussed and weighed.