Strong evidence in support of our claim includes: first, the increased expression of MANF correlated with synapse loss in the hippocampus of AD mice; second, the ectopic expression of MANF in the hippocampus led to synapse loss and behavioral deficits that are reminiscent of AD mice; third, increasing or decreasing MANF expression exacerbated or ameliorated the synaptic pathology in AD mice. Here, MANF is linked to Alzheimer disease.