One mechanistic role for RARα signaling in preventing amyloid-β accumulation at the onset of Alzheimer's disease is by increasing Notch related α-secretase activity via a direct induction of ADAM10, and Alzheimer's-like defects are indeed suppressed by RARα agonists in a transgenic mouse model [103]. Here, RARA is linked to early-onset autosomal dominant Alzheimer disease.