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

N. Ghenimi Rahab, S. Alfos, A. Redonnet, P. Higueret, V. Pallet, V. Enderlin
Journal of Neuroendocrinology. 2010-04-01; :
DOI: 10.1111/j.1365-2826.2010.02002.x

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1. J Neuroendocrinol. 2010 Aug;22(8):951-9. doi: 10.1111/j.1365-2826.2010.02002.x.
Epub 2010 Apr 9.

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

Ghenimi N(1), Alfos S, Redonnet A, Higueret P, Pallet V, Enderlin V.

Author information:
(1)Université de Bordeaux, Unité de Nutrition et Neurosciences, Avenue des
Facultés, Talence, France.

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 beta-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
(TRalpha1 and TRbeta) and the expression of some APP processing indicators (i.e.
APP, ADAM 10, BACE and PS1). The activity of secretases and Abeta 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 Abeta peptides. In
this area of the brain, modification in the non-amyloidogenic pathway of APP
processing characterised by alpha-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.

DOI: 10.1111/j.1365-2826.2010.02002.x
PMID: 20403092 [Indexed for MEDLINE]

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