Alzheimer's disease and angiogenesis

In their Hypothesis (Feb 15, p 605),1Vagnucci Jr, AH Li WW Alzheimer's disease and angiogenesis.Lancet. 2003; 361: 605-608Summary Full Text Full Text PDF PubMed Scopus (239) Google Scholar Anthony Vagnucci and William Li propose that Alzheimer's disease is mediated by pathological angiogenesis, a hypothesis that explains the puzzle posed by seemingly unrelated drugs that confer protection against the disease. One important issue they did not address, however, is a possible role of hypovitaminosis D in disease development. Epidemiological data lend support to the notion that hypovitaminosis D is present in patients with Alzheimer's disease.2Sato Y Asoh T Oizumi K High prevalence of vitamin D deficiency and reduced bone mass in elderly women with Alzheimer's disease.Bone. 1998; 23: 555-557Summary Full Text Full Text PDF PubMed Scopus (125) Google Scholar Furthermore, vitamin D receptor mRNA concentrations are reduced in the brains of patients,3Sutherland MK Somerville MJ Yoong LK Bergeron C Haussler MR McLachlan DR Reduction of vitamin D hormone receptor mRNA levels in Alzheimer as compared to Huntington hippocampus: correlation with calbindin-28k mRNA levels.Brain Res Mol Brain Res. 1992; 13: 239-250Crossref PubMed Scopus (169) Google Scholar which is suggestive of hypovitaminosis D. Low dietary cholecalciferol (vitamin D3) and calcium supply reduce vitamin D receptor mRNA expression in vivo,4Sandgren ME DeLuca HF Serum calcium and vitamin D regulate 1, 25-dihydroxyvitamin D3 receptor concentration in rat kidney in vivo.Proc Natl Acad Sci USA. 1990; 87: 4312-4314Crossref PubMed Scopus (66) Google Scholar causing resistance to calcitriol. Loss of vitamin D receptor function somehow interferes with the otherwise normal ability of calcitriol to exert negative feedback suppression on 1α-calcidiol-hydroxylase, thereby leading to high circulating levels of calcitriol, a somewhat confusing but intriguing mirror of calcitriol resistance in hypovitaminosis D.4Sandgren ME DeLuca HF Serum calcium and vitamin D regulate 1, 25-dihydroxyvitamin D3 receptor concentration in rat kidney in vivo.Proc Natl Acad Sci USA. 1990; 87: 4312-4314Crossref PubMed Scopus (66) Google Scholar Furthermore, calcitriol is synthesised in the brain from its precursor, is required for nerve growth factor and neurotransmitter synthesis, protects the brain cells against toxic agents, and inhibits brain ageing in animals. Finally, calcitriol inhibits angiogenesis by specifically inducing apoptosis of sprouting endothelial cells.5Mantell DJ Owens PE Bundred NJ Mawer EB Canfield AE 1 alpha, 25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo.Circ Res. 2000; 87: 214-220Crossref PubMed Scopus (425) Google Scholar The hypothesis and these findings thus point to a natural role of vitamin D in the protection of the brain against development of Alzheimer's disease, at least in a subgroup of predisposed individuals. Alzheimer's disease and angiogenesisAuthors' reply Full-Text PDF