Special Issue: Alzheimer's disease

Abstract

More than 45 million people worldwide have Alzheimer's disease (AD), a deterioration of memory and other cognitive domains that leads to death within 3 to 9 years after diagnosis. The principal risk factor for AD is age. As the aging population increases, the prevalence will approach 131 million cases worldwide in 2050. AD is therefore a global problem creating a rapidly growing epidemic and becoming a major threat to healthcare in our societies. It has been more than 20 years since it was first proposed that the neurodegeneration in AD may be caused by deposition of amyloid-β (Aβ) peptides in plaques in brain tissue. According to the amyloid hypothesis, accumulation of Aβ peptides, resulting from a chronic imbalance between Aβ production and Aβ clearance in the brain, is the primary influence driving AD pathogenesis. Current available medications appear to be able to produce moderate symptomatic benefits but not to stop disease progression. The search for biomarkers as well as novel therapeutic approaches for AD has been a major focus of research. Recent findings, however, show that neuronal-injury biomarkers are independent of Aβ suggesting epigenetic modifications, gene-gene and/or gene-environment interactions in the disease etiology, and calling for reconsideration of the pathological cascade and assessment of alternative therapeutic strategies. In addition, recent research results regarding the expression of the β-amyloid precursor protein (APP) gene resulting in the presence of various APP-mRNA isoforms and their quantification, especially for identifying the most abundant one that may decisive for the normal status or disease risk, have been reported. As such, a more complete understanding of AD pathogenesis will likely require greater insights into the physiological function of the β-amyloid precursor protein (APP).

Keywords: Alzheimer's disease; Amyloid-β (Aβ) peptides; Epigenetic modifications; Familial AD (FAD); Neurofibrillary tangles (NFTs); Sporadic AD (SAD); gene-gene and/or gene-environment interactions; β-amyloid precursor protein (APP).