What is it about?

This article introduces the concept of allostatic load and reviews the role of chronic stress in the development of pathological tau-related changes within the locus coeruleus (LC), a subcortical nucleus considered to be one of the first brain sites to show abnormalities related to Alzheimer's disease (AD). Over the past decade, there has been growing recognition that synaptotoxicity in AD may depend largely on the increase in hyperphosphorylated tau levels, beginning first in the LC. The LC innervates a vast network of brain regions and is the primary source of norepinephrine (NE) in the central nervous system. NE is a major modulator of neuroinflammation and neuroprotection, and degeneration of the LC-NE pathway in AD may drive other clinical and pathological manifestations of the disease.

Featured Image

Why is it important?

No published reviews have focussed specifically on the role of stress in tau-related LC-NE degeneration in AD. This is surprising, given that this pathway is critically involved in the brain's central stress response. Indeed, a significant literature underscores the link between AD pathology and life-long chronic stress. To address this important gap, in this article we provide a condensed overview of the literature on the role of chronic stress in LC degeneration, with a focus on aberrant accumulation of tau protein.


This stress-related perspective on the etiology of AD may shed some light on the observed sex differences in the prevalence of AD. Since women are roughly twice as likely to manifest stress-related mood disorders, the sex dimorphisms in the stress response within the HPA axis might explain the higher incidence of women with AD.

Donné Minné
Cape Peninsula University of Technology

Read the Original

This page is a summary of: Early Chronic Stress Induced Changes within the Locus Coeruleus in Sporadic Alzheimer’s Disease, Current Alzheimer Research, May 2023, Bentham Science Publishers,
DOI: 10.2174/1567205020666230811092956.
You can read the full text:



The following have contributed to this page