Stress and HPA Axis Dysfunction in Alzheimer’s Disease

Abstract

Memory loss is the most prominent clinical aspect of Alzheimer's disease(AD) but, as recent clinical evidence has been revealed, interveningwhen memory difficulties are already apparent does little to alter themorbidity and mortality of the disease. Therefore, risk factors thataccelerate the development of AD have recently received tremendousinterest. Among those risk factors, interrogation of stresshormones/glucocorticoids have been particularly impactful because stressis an inherent aspect of life and unavoidable. Heightened indices ofstress in mid-life predict greater risk for AD in late-life, stresshormone dysregulation in the aged increases AD vulnerability and higherlevels of circulating glucocorticoid in AD patients correlates withfaster cognitive decline. However, despite this evidence, the precisemechanism linking glucocorticoids and stress hormone to AD remainelusive.In this chapter, we provide an overview of thehypothalamus-pituitary-adrenal (HPA) axis, and how stress, dysregulationof stress hormones and HPA axis dysfunction are currently thought toplay a role in AD pathogenesis.