Alzheimer’s disease was first discovered in 1906 by Alois Alzheimer. It is a neurodegenerative disease characterized by the buildup of toxic amyloid plaque and intracellular neurofibrillary tangles, which results in the progressive loss of cognitive function and memory. Since its discovery, the disease has become a growing health concern, particularly in the developed world, where the ageing demographics have contributed to an increase in its prevalence and incidence. The earliest research into the disease focused on neurochemical analyses and resulted in the formulation of the cholinergic hypothesis. The mechanism of disease was explained as the degeneration of the cholinergic system and a reduction in acetylcholine. While much data supports this hypothesis, it fails to explain the accumulation of amyloid plaque, a hallmark of the disease. Analysis of the genetic factors in familial Alzheimer’s disease, and the discovery of the higher risk for Alzheimer’s disease amongst individuals with Down’s syndrome led to the more comprehensive amyloid cascade hypothesis. The failure of both amyloid centric drugs and cholinesterase inhibitors to have a significant impact on disease progression has caused some to have rejected both these hypotheses to focus on other possible causes. However, there is undoubtedly a wealth of data in support of both the cholinergic hypothesis and the amyloid cascade hypothesis. Understanding the functional relationship between the cholinergic system and the formation of beta amyloid plaques may lead to a greater understanding of the mechanism of disease and provide a target for more effective therapy.
Bordon, A. (2017). Molecular Mechanisms of Alzheimer’s Disease. The Science Journal of the Lander College of Arts and Sciences, 10 (2). Retrieved from http://touroscholar.touro.edu/cgi/viewcontent.cgi?article=1001&context=sjlcas