Adverse stress, hippocampal networks, and Alzheimer's disease

Neuromolecular Med. 2010 Mar;12(1):56-70. doi: 10.1007/s12017-009-8107-9. Epub 2009 Nov 27.


Recent clinical data have implicated chronic adverse stress as a potential risk factor in the development of Alzheimer's disease (AD) and data also suggest that normal, physiological stress responses may be impaired in AD. It is possible that pathology associated with AD causes aberrant responses to chronic stress, due to potential alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Recent study in rodent models of AD suggests that chronic adverse stress exacerbates the cognitive deficits and hippocampal pathology that are present in the AD brain. This review summarizes recent findings obtained in experimental AD models regarding the influence of chronic adverse stress on the underlying cellular and molecular disease processes including the potential role of glucocorticoids. Emerging findings suggest that both AD and chronic adverse stress affect hippocampal neural networks in a similar fashion. We describe alterations in hippocampal plasticity, which occur in both chronic stress and AD including dendritic remodeling, neurogenesis, and long-term potentiation. Finally, we outline potential roles for oxidative stress and neurotrophic factor signaling as the key determinants of the impact of chronic stress on the plasticity of neural networks and AD pathogenesis.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cognition Disorders / pathology
  • Cognition Disorders / physiopathology
  • Cognition Disorders / therapy
  • Glucocorticoids / metabolism
  • Hippocampus / anatomy & histology*
  • Hippocampus / pathology
  • Hippocampus / physiology
  • Humans
  • Hypothalamo-Hypophyseal System / metabolism
  • Nerve Growth Factors / metabolism
  • Nerve Net / anatomy & histology*
  • Nerve Net / physiology
  • Neurogenesis / physiology
  • Neuronal Plasticity / physiology
  • Pituitary-Adrenal System / metabolism
  • Signal Transduction / physiology
  • Stress, Physiological / physiology*


  • Amyloid beta-Peptides
  • Glucocorticoids
  • Nerve Growth Factors