Alzheimer's disease (AD) is a progressive neurodegenerative disorder which is the principal cause of dementia throughout the world and the fourth cause of death in developed countries. The pathological hallmarks of this disease are regionalized neuronal dysfunction/death, accumulation of senile plaques extracellularly and neurofibrillary tangles (NFTs) intraneuronally. Several hypotheses have been put forth to explain the pathophysiology of this disease, including aberrant β-amyloid (Aβ) metabolism, hyperphosphorylation of cytoskeletal proteins, genetic predisposition (mutations in genes coding for presenilin-1 and -2 (PS-1 and PS-2) and amyloid precursor protein (APP), apolipoprotein E genotype, oxidative stress, excitotoxicity, inflammation and abnormal cell cycle re-entry. However, none of these hypotheses alone is sufficient to explain the diversity of biochemical and pathological abnormalities in AD. Currently, medications approved by the United States FDA for AD include acetylcholinesterase (AChE) inhibitors and memantine. However, these drugs provide only symptomatic relief and do not stop disease progression. The major focus of research now is to find novel therapeutic drug candidates targeting the underlying pathophysiological mechanisms. These therapeutic strategies include drugs targeting amyloid and tau pathology, immunotherapy, neurotransmitter replacement therapy, nutraceuticals and disease-modifying therapies. The main focus of this review is to provide new insight on the various mechanisms involved in the neuropathology of AD and shed light on current and future treatment strategies aimed at improving both cognitive deficits and halting the deadly neurodegenerative progression of the disease. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.
Mendeley saves you time finding and organizing research
Choose a citation style from the tabs below