Abstract: ?-secretase (BACE) is a biomarker for MCI and Alzheimer's disease. BACE1 protein level and the enzymatic activity level increase in the brain, and in the CSF in AD and MCI patients. Increased BACE1 levels in CSF are related to neuronal death and synaptic damages, which contribute to AD-related cognitive deficits. BACE1 inhibitors may be used as therapeutic compounds for clinical use for the disease treatment and prevention. Use of Thalidomide, an effective BACE1 inhibitor, reduces the BACE1 enzymetic activity and protein levels, and the A? production that marks the neurodegenerative progression associated with AD.