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.