Affiliation:
1. Applied Microbial & Health Biotechnology Institute, Cape Peninsula University of Technology, Cape Town, 7535,
South Africa
2. Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, 7535,
South Africa
Abstract
Abstract:
Chronic exposure to stress throughout the lifespan has been the focus of many studies
on Alzheimer's disease (AD) because of the similarities between the biological mechanisms involved
in chronic stress and the pathophysiology of AD. In fact, the earliest abnormality associated
with the disease is the presence of phosphorylated tau protein in locus coeruleus neurons, a brain
structure highly responsive to stress and perceived threat. Here, we introduce allostatic load as a
useful concept for understanding many of the complex, interacting neuropathological changes involved
in the AD degenerative process. In response to chronic stress, aberrant tau proteins that begin
to accumulate within the locus coeruleus decades prior to symptom onset appear to represent a
primary pathological event in the AD cascade, triggering a wide range of interacting brain changes
involving neuronal excitotoxicity, endocrine alterations, inflammation, oxidative stress, and amyloid
plaque exacerbation. While it is acknowledged that stress will not necessarily be the major precipitating
factor in all cases, early tau-induced changes within the locus coeruleus-norepinephrine
pathway suggests that a therapeutic window might exist for preventative measures aimed at managing
stress and restoring balance within the HPA axis.
Funder
National Research Foundation of South Africa
Oppenheimer Memorial Trust
Publisher
Bentham Science Publishers Ltd.
Subject
Neurology (clinical),Neurology