TABLE 1.

Candidate Neurodegenerative Mechanisms in AD and Corresponding Therapeutic Neuroprotective Approaches

Target Mechanism	Examples of Corresponding Therapeutic or Potential Therapeutic Development
Aβ interaction with binding targets	Neurotrophin small molecule mimetics binding to p75NTR might block Aβ-p75NTR mediated toxicity
Activation of stress kinase/JNK signaling	CEP-1347 inhibitor of stress kinase activation in clinical trials for Parkinson’s disease
	Neurotrophin signaling blocks stress kinase signaling
Excessive tau phosphorylation and microtubule instability	GSK-3 inhibitors under development
	Valproate in AD trial underway
	Microtubule stabilizing drugs under development
Caspase activation	Minocycline caspase inhibitor in trials for ALS
Loss of synapses, neuronal death	Trial underway in which NGF-secreting fibroblasts are grafted to basal forebrain
	Neurotrophin mimetics under development
Loss of cholinergic function	ACIs in clinical use
	M1 agonists such as talsaclidine in clinical trials
	Neurotrophin mimetics under development
Generation of ROS	Vitamin E in trials for MCI
	Various antioxidants in MCI/AD trials
	Clioquinol metal chelator completed phase II trial
Glutamate excitotoxicity	Memantine NMDA uncompetitive antagonist in use in Europe for AD with FDA approval in US pending
	Other NMDA modulators under development