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Many biological processes in which the &gt;60 human 2OGDD are involved are altered in AD patient brains, raising the question as to whether 2OGDD are involved in the transition from normal aging to AD. Here we give an overview of human 2OGDD and critically discuss their potential roles in AD, highlighting possible relationships with synapse dysfunction\/loss. 2OGDD may regulate neuronal\/glial differentiation through enzyme activity\u2010dependent mechanisms and modulation of their activity has potential to protect against synapse loss. Work linking 2OGDD and AD is at an early stage, especially from a therapeutic perspective; we suggest integrated pathology and in vitro discovery research to explore their roles in AD is merited. We hope to help enable long\u2010term research on the roles of 2OGDD and, more generally, oxygen\/hypoxia in AD. 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