Pathophysiology of Alzheimer's Disease

Alzheimer's disease (AD) is a common cause of dementia in elderly people that is accompanied by progressive cognitive decline and memory loss. The pathologic hallmarks of AD are synaptic and neuronal degeneration together with extracellular senile plaques containing amyloid-beta (Aβ) and the intracellular neurofibrillary tangles (NFTs) in the hippocampus and other cortical regions. Amyloid-beta peptide is believed to have a pivotal role in the pathogenesis of AD as a major component of the senile plaques. It acts as a trigger key of AD and is considered as the principal toxic factor in the pathogenesis of the disease. Accumulation of amyloid β protein (Aβ), a main component of the senile plaques, in the brain initiates a cascade of events that ultimately lead to neuronal dysfunction and cognitive deficits. Other proposed mechanisms for AD include impairment in cholinergic function, oxidative stress, inflammatory agents and glutamate-mediated excitotoxicity. AD is characterized neuropathologically by impaired cholinergic function, increased oxidative stress, neuroinflammation, neuronal cell death, synapses loss, cortical atrophy, deficiencies in steroid hormones and appearance of glutamate-mediated excitotoxicity.