Adult-onset hypothyroidism induces the amyloidogenic pathway of amyloid precursor protein processing in the rat hippocampus

N. Ghenimi, S. Alfos, A. Redonnet, P. Higueret, V. Pallet, Valerie Enderlin

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Thyroid dysfunction and dementia are conditions that become more prevalent with advancing age. Localised hypothyroidism of the central nervous system has been sugested in some patients with Alzheimer's disease. We investigated the consequence of adult-onset hypothyroidism on β-amyloid precursor protein (APP) degrading pathways in rats treated with propylthiouracyl over a period of 5 weeks. We evaluated the amount of 3,5,3′-triiodothyronine nuclear receptors (TRα1 and TRβ) and the expression of some APP processing indicators (i.e. APP, ADAM 10, BACE and PS1). The activity of secretases and Aβ peptides has been also quantified. The results obtained show that hypoactivity of the thyroid signalling pathway in the hippocampus induced an increase in the APP770-751/APP695 ratio accompanied by a modification in the amyloidogenic pathway for APP processing, leading to an increased amount of Aβ peptides. In this area of the brain, modification in the non-amyloidogenic pathway of APP processing characterised by α-secretase activity was only approximately 10% in hypothyroid rats compared to control rats. We suggest that hypothyroidism, which becomes more prevalent with advancing age, increased the vulnerability to the formation of amyloid deposits.

Original languageEnglish
Pages (from-to)951-959
Number of pages9
JournalJournal of Neuroendocrinology
Issue number8
Publication statusPublished - Aug 2010
Externally publishedYes


  • Adult
  • Amyloidogenic pathway of APP processing
  • Hippocampus
  • Hypothyroidism
  • Non-amyloidogenic pathway of APP processing
  • Triiodothyronine nuclear receptors

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience


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