Disruption of the retinoid signalling pathway causes a deposition of amyloid beta in the adult rat brain.
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 beta in the cerebral blood vessels. There is a downregulation of retinoic acid receptor alpha in the forebrain neurons of the retinoid-deficient rats and a loss of choline acetyl transferase expression, which precedes amyloid beta deposition. In neocortex of pathology samples of patients with Alzheimer's disease, the same retinoic acid receptor alpha 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.
MRC Centre for Developmental Neurobiology, New Hunt's House, King's College London, Guy's Campus, London SE1 1UL, UK. Jonathan.corcoran@kcl.ac.uk
Jonathan P T
JP
Corcoran
Po Lin
PL
So
Malcolm
M
Maden
D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D050697:Retinal Dehydrogenase; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction / Q000502:physiology*; D014212:Tretinoin / Q000008:administration & dosage / Q000502:physiology; D014802:Vitamin A Deficiency / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D016229:Amyloid beta-Peptides; C000607071:RARA protein, human; C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase