BACE1 and Alzheimer disease: While the amyloid cascade hypothesis of AD has come under scrutiny in the last decade due to the failure of many Aβ- and BACE1-directed potential therapies in the clinic [11], it is supported by the genetics underlying familial forms of the disease that enhance amyloid production [12,13], by identification of gene variants that confer protection against cognitive decline [14]; and by recent clinical findings that the amyloid-directed antibodies aducanumab (Aduhelm®), lecanemab (Lequembi®), and donanemab (Kisunla®) slow cognitive decline in early AD [[15], [16], [17], [18]].