Table 1.

Major drug targets based on the amyloid hypothesis

Target	+/−	Examples	Side effects of specific drug
APP synthesis	−	Posiphen; Antisense; siRNA	Limited! APP is redundant
β-secretase	−	CTS21166	BACE1 has multiple substrates
γ-secretase*	−	semagacestat	Multiple targets, Toxic substrate accumulation
α-secretase	+	Benzolactam	Complex and not yet defined. Target dependent
Aβ degradation	+	TPA, UPA	Limited! May be very specific.
Aβ clearance	+	ApoE, LRP	Complex and not yet defined. Target dependent
Aβ aggregation	−	PBT-2	Limited! May be very specific.
Vaccination	+	Vaccination; Passive immunization	Inflammation
Aβ toxicity	−	Anti-Tau; -oxidants; -inflammatory	Complex and not yet defined. Target dependent

+= Stimulate; −= Inhibit

^*Alternate hypothesis: Inhibitor may cause AD!