Table 1.

Summary of therapeutic modulations of secretase and amylin for AD.

Biomolecule	Therapeutic Mechanism	Synthetic Subtypes under Investigation	Status of Investigations
α-secretase	Activation	ADAM10 ADAM17 Gemfibrozil	Gemfibrozil Phase I Trial—2019 [110,111] Acitretin Phase II Trial—2018 [112] APH-1105 Phase II Trial—2021 [113] Epigallocatechin-Gallate Phase III—2021 [114]
β-secretase	Inhibition	BACE1 LY-2886721	AZD3293 Phase I Trial—2014 [115] LY-2886721 Phase II Trial—2018 [116] JNJ-54861911 Phase II Trial—2022 [117,118] CNP520 Phase II Trial [119] Verubecestat Phase III Trial—2019 [120]
γ-secretase	Inhibition	LY-450139 E2012 PF-308414	LY-450139 Phase III Trial—2019 [121] Semagacestat Phase III Trial—2014 [122] Avagacestat Phase II Trial—2015 [123] GSI-136 Phase I Trial—2010 [124] NGP-555 Phase I Trial—2016 [125]
Amylin	Agonist	Pramlintide acetate Exenatide	Exendin-4 Phase II Trial—2018 [126]