Premium
Disruption of the retinoid signalling pathway causes a deposition of amyloid β in the adult rat brain
Author(s) -
Corcoran Jonathan P. T.,
So Po Lin,
Maden Malcolm
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2004.03563.x
Subject(s) - retinoid , retinoic acid , endocrinology , medicine , downregulation and upregulation , forebrain , biology , neocortex , neuroscience , central nervous system , biochemistry , gene
We have disrupted the retinoid signalling pathway in adult rats by a dietary deficiency of vitamin A. After 1 year of this dietary deficiency, there was a deposition of amyloid β in the cerebral blood vessels. There is a downregulation of retinoic acid receptor α in the forebrain neurons of the retinoid‐deficient rats and a loss of choline acetyl transferase expression, which precedes amyloid β deposition. In neocortex of pathology samples of patients with Alzheimer's disease, the same retinoic acid receptor α deficit in the surviving neurons was observed. We have identified the retinoid‐synthesizing enzymes involved in this process, retinaldehyde dehydrogenase‐2 and class IV alcohol dehydrogenase, only the former is downregulated in patients with Alzheimer's disease. This suggests that retinoids are important for the maintenance of the adult nervous system and their loss may in part play a role in Alzheimer's disease.