Content area
Full Text
Received Jul 17, 2017; Revised Nov 24, 2017; Accepted Jan 1, 2018
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, with neuropathology characterized by the accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles. In 2016, Alzheimer’s Disease International, an organization founded to promote efforts to prevent and treat the disease, issued their World Alzheimer’s Report, which estimates that 46.8 million people worldwide were living with AD, with 131.5 million projected to be afflicted by 2050 [1]. Changes in demographic patterns, principally increasing life expectancy, with resulting increases in elderly populations, have resulted in a concomitant expansion of AD-afflicted individuals and an increased burden on national healthcare systems. According to Alzheimer’s Association, AD is the 6th leading cause of death in the USA, with 1 out of every 3 elderly people succumbing to it in 2016. In that year, the estimated fiscal cost of the disease was 236 billion dollars, which is forecast to increase to a trillion dollars annually by 2050. These factors notwithstanding, the development of effective countermeasures for AD remains elusive at the time of this writing [1].
Although comprehensively definitive descriptions of AD pathomechanisms remain undefined, some major contributing factors have been elucidated. For example, evidence of a signaling cascade triggered by amyloid deposits, resulting in neuroinflammation and microtubule-associated tau protein hyperphosphorylation, is a likely major underlying process contributing to AD pathogenesis [2]. An element of this phenomenon is amyloid precursor protein (APP), a transmembrane component of the outer membrane of the cell. Also, the mitochondria is cleaved by three enzymes α-, β-, and γ-secretases, with variable cleavage outcomes, determined by as-yet undefined factors. Exploration of this enzymatic activity reveals that cleavage by α-secretase prevents amyloid β-formation—and the main products of cleavage by β- and γ-secretases include Aβ40 and Aβ42, which are secreted extracellularly, and may form aggregations that contribute to neurological tissue damage [3–5].
Tau protein aggregation is promoted by amyloid β, which may directly or indirectly activate protein kinases, such as GSK3 and CDK5, via...