Constitutive 5-HT4R activity is involved in nonamyloidogenic APP cleavage by direct interaction with the α-secretase ADAM10, resulting in the production of sAPPα, which has neuroprotective effects.229, 230, 231, 232 Loss of 5-HT4R may therefore directly contribute to the pathogenesis of AD. The gene discussed is HTR4; the disease is Alzheimer disease.