title: Impact of Vitamin D on amyloid precursor protein processing and amyloid-β peptide degradation in Alzheimer's disease.
abstract: Ninety percent of the elderly population has a vitamin D hypovitaminosis, and several lines of evidence suggest that there might be a potential causal link between Alzheimer's disease (AD) and a non-sufficient supply with vitamin D. However, the mechanisms linking AD to vitamin D have not been completely understood. The aim of our study is to elucidate the impact of 25(OH) vitamin D3 on amyloid precursor protein processing in mice and N2A cells utilizing very moderate and physiological vitamin D hypovitaminosis in the range of 20-30% compared to wild-type mice. We found that already under such mild conditions, amyloid-β peptide (Aβ) is significantly increased, which is caused by an increased β-secretase activity and BACE1 protein level. Additionally, neprilysin (NEP) expression is downregulated resulting in a decreased NEP activity further enhancing the effect of decreased vitamin D on the Aβ level. In line with the in vivo findings, corresponding effects were found with N2A cells supplemented with 25(OH) vitamin D3. Our results further strengthen the link between AD and vitamin D3 and suggest that supplementation of vitamin D3 might have a beneficial effect in AD prevention.
authors.affiliation: Experimental Neurology, Saarland University, Homburg/Saar, Germany.
authors.forename: Marcus O W
authors.initials: MO
authors.lastname: Grimm
authors.forename: Johannes
authors.initials: J
authors.lastname: Lehmann
authors.forename: Janine
authors.initials: J
authors.lastname: Mett
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Zimmer
authors.forename: Sven
authors.initials: S
authors.lastname: Grösgen
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Stahlmann
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hundsdörfer
authors.forename: Viola J
authors.initials: VJ
authors.lastname: Haupenthal
authors.forename: Tatjana L
authors.initials: TL
authors.lastname: Rothhaar
authors.forename: Christian
authors.initials: C
authors.lastname: Herr
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.forename: Heike S
authors.initials: HS
authors.lastname: Grimm
authors.forename: Tobias
authors.initials: T
authors.lastname: Hartmann
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002762:Cholecalciferol / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014808:Vitamin D Deficiency / Q000150:complications / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002762:Cholecalciferol; D053829:Amyloid Precursor Protein Secretases