Current pharmacotherapy and putative disease-modifying therapy for Alzheimer's disease

Alzheimer's disease (AD) is an age-related neurodegenerative disease of the central nervous system correlated with the progressive loss of cognition and memory. beta-Amyloid plaques, neurofibrillary tangles and the deficiency in cholinergic neurotransmission constitute the major hallmarks of the AD. Two major hypotheses have been implicated in the pathogenesis of AD namely the cholinergic hypothesis which ascribed the clinical features of dementia to the deficit cholinergic neurotransmission and the amyloid cascade hypothesis which emphasized on the deposition of insoluble peptides formed due to the faulty cleavage of the amyloid precursor protein. Current pharmacotherapy includes mainly the acetylcholinesterase inhibitors and N-methyl-d-aspartate receptor agonist which offer symptomatic therapy and does not address the underlying cause of the disease. The disease-modifying therapy has garnered a lot of research interest for the development of effective pharmacotherapy for AD. beta and gamma-Secretase constitute attractive targets that are focussed in the disease-modifying approach. Potentiation of alpha-secretase also seems to be a promising approach towards the development of an effective anti-Alzheimer therapy. Additionally, the ameliorative agents that prevent aggregation of amyloid peptide and also the ones that modulate inflammation and oxidative damage associated with the disease are focussed upon. Development in the area of the vaccines is in progress to combat the characteristic hallmarks of the disease. Use of cholesterol-lowering agents also is a fruitful strategy for the alleviation of the disease as a close association between the cholesterol and AD has been cited. The present review underlines the major therapeutic strategies for AD with focus on the new developments that are on their way to amend the current therapeutic scenario of the disease.