Emerging amyloid beta (Ab) peptide modulators for the treatment of Alzheimer's disease (AD).

BACKGROUND

According to the 'amyloid cascade hypothesis' of Alzheimer's disease (AD), abnormal processing of beta-amyloid precursor protein (betaAPP) into toxic amyloid beta (Abeta)-peptides is central to the etiopathology of this uniquely human brain disorder.

OBJECTIVE

To review current AD drugs, pharmacological approaches and strategies aimed at modulating Abeta-peptide generation and/or aggregation in the treatment of AD.

METHODS

Data searches at various websites: Alzheimer Research Forum; individual drug company databases; Medline; Pharmaprojects database; unpublished research; inter-University research communications.

RESULTS/CONCLUSION: Considerable research effort has focused on secretase-mediated mechanisms of betaAPP processing, and the latest pharmacological strategies have used selective Abeta-peptide-lowering agents (SALA) to provide therapeutic benefit against Abeta-initiated neurodegenerative pathology. Currently, dedicated anticholinesterase, glutamatergic agonist and Abeta-peptide immunization have had little impact in the clinical treatment of AD. One unexpected benefit of statins (HMG-CoA inhibitors), besides their cholesterol lowering abilities, has been their ancillary effects in potentiating the enzymatic mechanisms that generate Abeta-peptides. The long-term benefits or complications of statin-based therapies for use in the clinical management of AD are not known.