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A key feature of AD is synapse loss. ApoE4, amyloid\u2010\u03b2 (A\u03b2)\u2010peptides, phospho\u2010tau, and neuroinflammation are thought to induce AD pathogenesis, but their molecular mechanisms are incompletely understood. Free A\u03b2\u2010peptides whose levels decrease in AD are synaptogenic, whereas aggregating A\u03b2\u2010peptides that accumulate in AD are synaptotoxic. It is unclear whether AD is driven primarily by the loss of free A\u03b2, the increase of aggregated A\u03b2, or both, nor do we know how ApoE4 affects synapses. Therefore, understanding the molecular pathways mediating synapse loss in AD is a priority in developing new therapies. 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