Skip to main content

Advertisement

SpringerLink
Log in

Vitamin D basis of Alzheimer’s disease: from genetics to biomarkers

  • Short Review Article
  • Published:
Hormones Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder seen mostly in the elderly population. While to date AD research has focused on either neurochemical disruptions, genetic studies, or the pathological hallmarks, little has been done to establish a novel approach that would encompass all three aspects, one that would overcome the current barriers in AD research and determine the cause of AD and, eventually, discover a treatment. Meanwhile, there have been strong indications in recent years that vitamin D, a secosteroid hormone, and its receptors are fundamentally involved in neurodegenerative mechanisms. Observational studies have pointed to vitamin D deficiency as a genetic risk factor for AD, Parkinson’s disease (PD), vascular dementia, and multiple sclerosis (MS), as well as other neurological disorders, brought about by alterations in genes involved in metabolism, transportation, and actions of vitamin D. Molecular studies have demonstrated that vitamin D treatments prevent amyloid production while also increasing its clearance from the brain in AD. Finally, recent vitamin D intervention studies have reported significant improvement in cognitive performance in subjects with senile dementia, mild cognitive impairment, and AD. This review aims to describe how a vitamin D research strategy, fully integrating all aspects of present-day AD research, would elucidate the genetic, molecular, and biochemical background of the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Rocca WA, Hofmann A, Brayne C, Breteler MM, Clarke M, Copeland JR, Dartigues JF, Engedal K, Hagnell O, Heeren TJ (1991) Frequency and distribution of Alzheimer’s disease in Europe: a collaborative study of 1980-1990 prevalence findings. The EURODEM-Prevalance Research Group. Ann Neurol 30:381–390

    Article  CAS  PubMed  Google Scholar 

  2. Emilien G, Durlach C, Minaker KL, Winblad B, Gauthier S, Maloteaux JM (2004) Introduction. In: Alzheimer Disease Neuropsychology and Pharmacology. Brighauser Verlag, Basel, pp x–xxiv

    Chapter  Google Scholar 

  3. Hardy J (1997) Amyloid, the presenilins and Alzheimer’s disease. Trends Neurosci 20:154–159

    Article  CAS  PubMed  Google Scholar 

  4. Hardy J (2006) A hundred years of Alzheimer’s disease research. Neuron 52(1):3–13

    Article  CAS  PubMed  Google Scholar 

  5. Alzheimer's Association (2012) 2012 Alzheimer’s disease facts and figures. Alzheimers Dement 8(2):131–168

    Article  Google Scholar 

  6. Gezen-Ak D, Yilmazer S, Dursun E (2014) Why vitamin D in Alzheimer’s disease? The hypothesis. J Alzheimers Dis 40(2):257–269

    Article  CAS  PubMed  Google Scholar 

  7. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G (2016) Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev 96(1):365–408

    Article  CAS  PubMed  Google Scholar 

  8. Cekic M, Sayeed I, Stein DG (2009) Combination treatment with progesterone and vitamin d hormone may be more effective than monotherapy for nervous system injury and disease. Front Neuroendocrinol 30:158–172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D (2002) New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 13(3):100–105

    Article  CAS  PubMed  Google Scholar 

  10. Holick M (1995) Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications. Bone 17:107–111

    Article  Google Scholar 

  11. Dursun E, Alaylioglu M, Bilgic B, Hanagasi H, Lohmann E, Atasoy IL, Candas E, Araz OS, Onal B, Gurvit H, Yilmazer S, Gezen-Ak D (2016) Vitamin D deficiency might pose a greater risk for ApoEvarepsilon4 non-carrier Alzheimer’s disease patients. Neurol Sci 37(10):1633–1643

    Article  PubMed  Google Scholar 

  12. Gezen-Ak D, Alaylioglu M, Genc G, Gunduz A, Candas E, Bilgic B, Atasoy IL, Apaydin H, Kiziltan G, Gurvit H, Hanagasi H, Ertan S, Yilmazer S, Dursun E (2017) GC and VDR SNPs and vitamin D levels in Parkinson’s disease: the relevance to clinical features. NeuroMolecular Med 19(1):24–40

    Article  CAS  PubMed  Google Scholar 

  13. Gezen-Ak D, Atasoy IL, Candas E, Alaylioglu M, Yilmazer S, Dursun E (2017) Vitamin D receptor regulates amyloid beta 1-42 production with protein disulfide isomerase A3. ACS Chem Neurosci 8(10):2335–2346

    Article  CAS  PubMed  Google Scholar 

  14. Annweiler C, Dursun E, Feron F, Gezen-Ak D, Kalueff AV, Littlejohns T, Llewellyn D, Millet P, Scott T, Tucker KL, Yilmazer S, Beauchet O (2016) Vitamin D and cognition in older adults: international consensus guidelines. Geriatr Psychol Neuropsychiatr Vieil 14(3):265–273

    PubMed  Google Scholar 

  15. Annweiler C, Dursun E, Feron F, Gezen-Ak D, Kalueff AV, Littlejohns T, Llewellyn DJ, Millet P, Scott T, Tucker KL, Yilmazer S, Beauchet O (2015) ‘Vitamin D and cognition in older adults’: updated international recommendations. J Intern Med 277(1):45–57

    Article  CAS  PubMed  Google Scholar 

  16. Poduslo SE, Yin X (2001) Chromosome 12 and late onset Alzheimer’s disease. Neurosci Lett 310:188–190

    Article  CAS  PubMed  Google Scholar 

  17. Blacker D, Wilcox MA, Laird NM, Rodes L, Horvath SM, Go RC, Perry R, Watson B Jr, Bassett SS, McInnis MG, Albert MS, Hyman BT, Tanzi RE (1998) Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat Genet 19:357–360

    Article  CAS  PubMed  Google Scholar 

  18. Hollenbach E, Ackermann S, Hyman BT, Rebeck GW (1998) Confirmation of an association between a polymorphism in exon 3 of the low-density lipoprotein receptor-related protein gene and Alzheimer’s disease. Neurology 50:1905–1907

    Article  CAS  PubMed  Google Scholar 

  19. Luedecking-Zimmer E, DeKosky S, Nebes R, Kamboh I (2003) Association of the 3’UTR transcription factor LBP-1c/CP2/LSF polymorphism with late-onset Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 117B:114–117

    Article  PubMed  Google Scholar 

  20. Beecham GW, Martin ER, Li YJ, Slifer MA, Gilbert JR, Haines JL, Pericak-Vance MA (2009) Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. Am J Hum Genet 84:35–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gezen-Ak D, Dursun E, Ertan T, Hanagasi H, Gurvit H, Emre M, Eker E, Ozturk M, Engin F, Yilmazer S (2007) Association between vitamin D receptor gene polymorphism and Alzheimer’s disease. Tohoku J Exp Med 212(3):275–282

    Article  CAS  PubMed  Google Scholar 

  22. Dursun E, Gezen- Ak D, Eker E, Ertan T, Engin F, Hanagasi H, Gürvit H, Emre M, Yilmazer S (2008) Presenilin-1 gene intronic polymorphism and late-onset Alzheimer’s disease. J Geriatr Psychiatry Neurol 21:268–273

    Article  PubMed  Google Scholar 

  23. Dursun E, Gezen-Ak D, Ertan T, Bilgiç B, Gürvit H, Emre M, Eker E, Engin F, Uysal Ö, Yılmazer S (2009) Interleukin-1α–889 C/T polymorphism in Turkish patients with late-onset Alzheimer’s disease. Dement Geriatr Cogn Disord 27:82–87

    Article  CAS  PubMed  Google Scholar 

  24. Gezen-Ak D, Kahraman H, Dursun E, Süsleyici Duman B, Erensoy N, Alagöl F, Yılmazer S (2005) Polymorphisms at the ligand binding sites of vitamin D receptor gene and osteomalacia. Dis Markers 21:191–197

    Article  Google Scholar 

  25. Gezen-Ak D, Dursun E, Bilgic B, Hanagasi H, Ertan T, Gurvit H, Emre M, Eker E, Ulutin T, Uysal O, Yilmazer S (2012) Vitamin D receptor gene haplotype is associated with late-onset Alzheimer’s disease. Tohoku J Exp Med 228(3):189–196

    Article  CAS  PubMed  Google Scholar 

  26. Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338(2):143–156

    Article  CAS  PubMed  Google Scholar 

  27. Kuningas M, Mooijaart SP, Jolles J, Slagboom PE, Westendorp RGJ, Van Heemst D (2009) VDR gene variants associate with cognitive function and depressive symptoms in old age. Neurobiol Aging 30:466–473

    Article  CAS  PubMed  Google Scholar 

  28. Beydoun MA, Ding EL, Beydoun HA, Tanaka T, Ferrucci L, Zonderman AB (2012) Vitamin D receptor and megalin gene polymorphisms and their associations with longitudinal cognitive change in US adults. Am J Clin Nutr 95:163–178

    Article  CAS  PubMed  Google Scholar 

  29. Lehmann DJ, Refsum H, Warden DR, Medway C, Wilcock GK, Smith DA (2011) The vitamin D receptor gene is associated with Alzheimer’s disease. Neurosci Lett 504:79–82

    Article  CAS  PubMed  Google Scholar 

  30. Butler MW, Burt A, Edwards TL, Zuchner S, Scott WK, Martin ER, Vance JM, Wang L (2011) Vitamin D receptor gene as a candidate gene for Parkinson disease. Ann Hum Genet 75(2):201–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Vargas T, Bullido MJ, Martinez-Garcia A, Antequera D, Clarimon J, Rosich-Estrago M, Martin-Requero A, Mateo I, Rodriguez-Rodriguez E, Vilella-Cuadrada E, Frank A, Lleo A, Molina-Porcel L, Blesa R, Combarros O, Gomez-Isla T, Bermejo-Pareja F, Valdivieso F, Carro E (2010) A megalin polymorphism associated with promoter activity and Alzheimer’s disease risk. Am J Med Genet B Neuropsychiatr Genet 153B(4):895–902

    CAS  PubMed  Google Scholar 

  32. Wang LL, Pan XL, Wang Y, Tang HD, Deng YL, Ren RJ, Xu W, Ma JF, Wang G, Chen SD (2011) A single nucleotide polymorphism in LRP2 is associated with susceptibility to Alzheimer’s disease in the Chinese population. Clin Chim Acta 412(3–4):268–270

    Article  CAS  PubMed  Google Scholar 

  33. Sutherland MK, Somerville MJ, Yoong LK, Bergeron C, Haussler MR, McLachlan DR (1992) 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 13(3):239–250

    Article  CAS  PubMed  Google Scholar 

  34. Dursun E, Gezen-Ak D, Yilmazer S (2011) A novel perspective for Alzheimer’s disease: vitamin D receptor suppression by amyloid-beta and preventing the amyloid-beta induced alterations by vitamin D in cortical neurons. J Alzheimers Dis 23(2):207–219

    Article  CAS  PubMed  Google Scholar 

  35. Dursun E, Gezen-Ak D, Yilmazer S (2013) Beta amyloid suppresses the expression of the vitamin d receptor gene and induces the expression of the vitamin d catabolic enzyme gene in hippocampal neurons. Dement Geriatr Cogn Disord 36(1–2):76–86

    Article  CAS  PubMed  Google Scholar 

  36. Gezen-Ak D, Dursun E, Yilmazer S (2013) Vitamin D inquiry in hippocampal neurons: consequences of vitamin D-VDR pathway disruption on calcium channel and the vitamin D requirement. Neurol Sci 34(8):1453–1458

    Article  PubMed  Google Scholar 

  37. Gezen-Ak D, Dursun E, Yilmazer S (2013) The effect of vitamin D treatement on nevre growth factor release (NGF) in hippocampal neurons. Arch Neuropsych. https://doi.org/10.4274/npa.y7076

  38. Dursun E, Gezen-Ak D, Yilmazer S (2013) The influence of vitamin D treatment on the inducible nitric oxide synthase expression in primary hippocampal neurons. Arch Neuropsych 51(2):163–168. https://doi.org/10.4274/npa.y7089

  39. Dursun E, Gezen-Ak D (2017) Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin. PLoS One 12(11):e0188605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dursun E, Gezen-Ak D, Yilmazer S (2013) A new mechanism for amyloid-beta induction of iNOS: vitamin D-VDR pathway disruption. J Alzheimers Dis 36(3):459–474

    Article  CAS  PubMed  Google Scholar 

  41. Gezen-Ak D, Dursun E, Yilmazer S (2011) The effects of vitamin D receptor silencing on the expression of LVSCC-A1C and LVSCC-A1D and the release of NGF in cortical neurons. PLoS One 6(3):e17553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gezen-Ak D, Atasoy IL, Candas E, Alaylioglu M, Dursun E (2018) The transcriptional regulatory properties of amyloid beta 1-42 may include regulation of genes related to neurodegeneration. NeuroMolecular Med 20(3):363–375

    Article  CAS  PubMed  Google Scholar 

  43. Mizwicki MT, Menegaz D, Zhang J, Barrientos-Durán A, Tse S, Cashman JR, Griffin PR, Fiala M (2011) Genomic and nongenomic signaling induced by 1α,25(OH)2-vitamin D3 promotes the recovery of amyloid-β phagocytosis by Alzheimer’s disease macrophages. J Alzheimers Dis 29(1):51–62

    Article  CAS  Google Scholar 

  44. Grimm MOW, Thiel A, Lauer AA, Winkler J, Lehmann J, Regner L, Nelke C, Janitschke D, Benoist C, Streidenberger O, Stotzel H, Endres K, Herr C, Beisswenger C, Grimm HS, Bals R, Lammert F, Hartmann T (2017) Vitamin D and its analogues decrease amyloid-beta (Abeta) formation and increase Abeta-degradation. Int J Mol Sci 18(12)

  45. Landel V, Stephan D, Cui X, Eyles D, Feron F (2017) Differential expression of vitamin D-associated enzymes and receptors in brain cell subtypes. J Steroid Biochem Mol Biol 177:129–134. https://doi.org/10.1016/j.jsbmb.2017.09.008

  46. Berridge MJ (2017) Vitamin D and depression: cellular and regulatory mechanisms. Pharmacol Rev 69(2):80–92

    Article  CAS  PubMed  Google Scholar 

  47. Yu J, Gattoni-Celli M, Zhu H, Bhat NR, Sambamurti K, Gattoni-Celli S, Kindy MS (2011) Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AβPP transgenic mice. J Alzheimers Dis 25(2):295–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. F’eron F, Burne THJ, Brown J, Smith E, McGrath JJ, Mackay-Sima A, Eyles DW (2005) Developmental Vitamin D3 deficiency alters the adult rat brain. Brain Res Bull 65(2):141–148

    Article  CAS  Google Scholar 

  49. Fernandes de Abreu DA, Eyles D, Féron F, Vitamin D (2009) a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology 34(1):265–277

    Article  CAS  Google Scholar 

  50. Norman AW, Bouillon R (2010) Vitamin D nutritional policy needs a vision for the future. Exp Biol Med (Maywood) 235(9):1034–1045

    Article  CAS  Google Scholar 

  51. Khazai N, Judd SE, Tangpricha V (2008) Calcium and vitamin D: skeletal and extraskeletal health. Curr Rheumatol Rep 10:110–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Annweiler C, Schott AM, Allali G, Bridenbaugh SA, Kressig RW, Allain P, Herrmann FR, Beauchet O (2010) Association of vitamin D deficiency with cognitive impairment in older women: cross-sectional study. Neurology 74(1):27–32

    Article  CAS  PubMed  Google Scholar 

  53. Cherniack EP, Florez H, Roos BA, Troen BR, Levis S (2008) Hypovitaminosis D in the elderly: from bone to brain. J Nutr Health Aging 12(6):366–373

    Article  CAS  PubMed  Google Scholar 

  54. Evatt ML, DeLong MR, Khazai N, Rosen A, Triche S, Tangpricha V (2008) Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol 65(10):1348–1352

    Article  PubMed  PubMed Central  Google Scholar 

  55. Llewellyn DJ, Langa KM, Lang IA (2009) Serum 25-hydroxyvitamin D concentration and cognitive impairment. J Geriatr Psychiatry Neurol 22(3):188–195

    Article  PubMed  Google Scholar 

  56. Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, Ferrucci L, Melzer D, Vitamin D (2010) Risk of cognitive decline in elderly persons. Arch Intern Med 170(13):1135–1141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. McCann J, Ames BN (2008) Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction? FASEB J 22:982–1001

    Article  CAS  PubMed  Google Scholar 

  58. Wilkins CH, Sheline YI, Roe CM, Birge SJ, Morris JC (2006) Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry 14:1032–1040

    Article  PubMed  Google Scholar 

  59. Oudshoorn C, Mattace-Raso FUS, van der Velde N, Colin EM, van der Cammen TJM (2008) Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 25:539–543

    Article  CAS  PubMed  Google Scholar 

  60. Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Beauchet O (2012) Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: a 7-year longitudinal study. Dement Geriatr Cogn Disord 32:273–278

    Article  CAS  Google Scholar 

  61. Annweiler C, Fantino B, Schott AM, Krolak-Salmon P, Allali G, Beauchet O (2012) Vitamin D insufficiency and mild cognitive impairment: cross-sectional association. Eur J Neurol 19(7):1023–1029

    Article  CAS  PubMed  Google Scholar 

  62. Annweiler C, Montero-Odasso M, Llewellyn DJ, Richard-Devantoy S, Duque G, Beauchet O (2013) Meta-analysis of memory and executive dysfunctions in relation to vitamin D. J Alzheimers Dis 37(1):147–171

    Article  CAS  PubMed  Google Scholar 

  63. Annweiler C, Llewellyn DJ, Beauchet O (2013) Low serum vitamin D concentrations in Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis 33(3):659–674

    Article  CAS  PubMed  Google Scholar 

  64. Afzal S, Bojesen SE, Nordestgaard BG (2013) Reduced 25-hydroxyvitamin D and risk of Alzheimer’s disease and vascular dementia. Alzheimers Dement 10(3):296–302. https://doi.org/10.1016/j.jalz.2013.05.1765

  65. Masoumi A, Goldenson B, Ghirmai S, Avagyan H, Zaghi J, Abel K, Zheng X, Espinosa-Jeffrey A, Mahanian M, Liu PT, Hewison M, Mizwickie M, Cashman J, Fiala M (2009) 1alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer’s disease patients. J Alzheimers Dis 17(3):703–717

    Article  CAS  PubMed  Google Scholar 

  66. Fiala M, Mizwicki MT (2011) Neuroprotective and immune effects of active forms of vitamin D3 and docosahexaenoic acid in Alzheimer disease patients. Functional Foods in Health and Disease (12):545–554

  67. Annweiler C, Fantino B, Parot-Schinkel E, Thiery S, Gautier J, Beauchet O (2011) Alzheimer’s disease--input of vitamin D with memantine assay (AD-IDEA trial): study protocol for a randomized controlled trial. Trials 12:230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Buell JS, Dawson-Hughes B, Scott TM, Weiner DE, Dallal GE, Qui WQ, Bergethon P, Rosenberg IH, Folstein MF, Patz S, Bhadelia RA, Tucker KL (2010) 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 74(1):18–26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sun Q, Pan A, Hu FB, Manson JE, Rexrode KM (2012) 25-Hydroxyvitamin D levels and the risk of stroke: a prospective study and meta-analysis. Stroke 43(6):1470–1477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Brondum-Jacobsen P, Nordestgaard BG, Schnohr P, Benn M (2013) 25-hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis. Ann Neurol 73(1):38–47

    Article  CAS  PubMed  Google Scholar 

  71. Tapiola T, Alafuzoff I, Herukka SK, Parkkinen L, Hartikainen P, Soininen H, Pirttila T (2009) Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol 66(3):382–389

    Article  PubMed  Google Scholar 

  72. Sjogren M, Andreasen N, Blennow K (2003) Advances in the detection of Alzheimer’s disease-use of cerebrospinal fluid biomarkers. Clin Chim Acta 332(1–2):1–10

    Article  CAS  PubMed  Google Scholar 

  73. Abdi F, Quinn JF, Jankovic J, McIntosh M, Leverenz JB, Peskind E, Nixon R, Nutt J, Chung K, Zabetian C, Samii A, Lin M, Hattan S, Pan C, Wang Y, Jin J, Zhu D, Li GJ, Liu Y, Waichunas D, Montine TJ, Zhang J (2006) Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. J Alzheimers Dis 9(3):293–348

    Article  CAS  PubMed  Google Scholar 

  74. Moon M, Song H, Hong HJ, Nam DW, Cha MY, Oh MS, Yu J, Ryu H, Mook-Jung I (2013) Vitamin D-binding protein interacts with Abeta and suppresses Abeta-mediated pathology. Cell Death Differ 20(4):630–638

    Article  CAS  PubMed  Google Scholar 

  75. Zhang J, Sokal I, Peskind ER, Quinn JF, Jankovic J, Kenney C, Chung KA, Millard SP, Nutt JG, Montine TJ (2008) CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases. Am J Clin Pathol 129:526–529

    Article  CAS  PubMed  Google Scholar 

  76. SanMartin CD, Henriquez M, Chacon C, Ponce DP, Salech F, Rogers NK, Behrens MI (2018) Vitamin D increases Abeta140 plasma levels and protects lymphocytes from oxidative death in mild cognitive impairment patients. Curr Alzheimer Res 15(6):561–569

    Article  CAS  PubMed  Google Scholar 

  77. Lemire P, Brangier A, Beaudenon M, Duval GT, Annweiler C (2018) Cognitive changes under memantine according to vitamin D status in Alzheimer patients: an exposed/unexposed cohort pilot study. J Steroid Biochem Mol Biol 175:151–156

    Article  CAS  PubMed  Google Scholar 

  78. Gangwar AK, Rawat A, Tiwari S, Tiwari SC, Narayan J, Tiwari S (2015) Role of vitamin-D in the prevention and treatment of Alzheimer’s disease. Indian J Physiol Pharmacol 59(1):94–99

    CAS  PubMed  Google Scholar 

  79. Chaves M, Toral A, Bisonni A, Rojas JI, Fernandez C, Garcia Basalo MJ, Matusevich D, Cristiano E, Golimstok A (2014) Treatment with vitamin D and slowing of progression to severe stage of Alzheimer’s disease. Vertex 25(114):85–91

    PubMed  Google Scholar 

  80. Littlejohns TJ, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PH, Fried L, Kestenbaum BR, Kuller LH, Langa KM, Lopez OL, Kos K, Soni M, Llewellyn DJ (2014) Vitamin D and the risk of dementia and Alzheimer disease. Neurology 83(10):920–928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Licher S, de Bruijn R, Wolters FJ, Zillikens MC, Ikram MA, Ikram MK (2017) Vitamin D and the risk of dementia: the Rotterdam study. J Alzheimers Dis 60(3):989–997

    Article  CAS  PubMed  Google Scholar 

  82. Jayedi A, Rashidy-Pour A, Shab-Bidar S (2018) Vitamin D status and risk of dementia and Alzheimer’s disease: a meta-analysis of dose-response. Nutr Neurosci 1–10. https://doi.org/10.1080/1028415X.2018.1436639

  83. Amadieu C, Lefevre-Arbogast S, Delcourt C, Dartigues JF, Helmer C, Feart C, Samieri C (2017) Nutrient biomarker patterns and long-term risk of dementia in older adults. Alzheimers Dement 13(10):1125–1132

    Article  PubMed  Google Scholar 

  84. Wang L, Hara K, Van Baaren JM, Price JC, Beecham GW, Gallins PJ, Whitehead PL, Wang G, Lu C, Slifer MA, Zuchner S, Martin ER, Mash D, Haines JL, Pericak-Vance MA, Gilbert JR (2012) Vitamin D receptor and Alzheimer’s disease: a genetic and functional study. Neurobiol Aging 33(8):1844 e1–1844 e9

    Article  CAS  Google Scholar 

  85. Lee YH, Kim JH, Song GG (2014) Vitamin D receptor polymorphisms and susceptibility to Parkinson’s disease and Alzheimer’s disease: a meta-analysis. Neurol Sci 35(12):1947–1953

    Article  PubMed  Google Scholar 

  86. Beydoun MA, Tajuddin SM, Dore GA, Canas JA, Beydoun HA, Evans MK, Zonderman AB (2017) Vitamin D receptor and megalin gene polymorphisms are associated with longitudinal cognitive change among African-American urban adults. J Nutr 147(6):1048–1062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Nathan C, Calingasan N, Nezezon J, Ding A, Lucia MS, La Perle K, Fuortes M, Lin M, Ehrt S, Kwon NS, Chen J, Vodovotz Y, Kipiani K, Beal MF (2005) Protection from Alzheimer’s-like disease in the mouse by genetic ablation of inducible nitric oxide synthase. J Exp Med 202(9):1163–1169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom PEM, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O’Banion MK, Pachter J, Pasinetti GP-SC, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Moore AH, O’Banion MK (2002) Neuroinflammation and anti-inflammatory therapy for Alzheimer’s disease. Adv Drug Deliv Rev 54:1627–1656

    Article  CAS  PubMed  Google Scholar 

  90. Lee YB, Nagai A, Kim SU (2002) Cytokines, chemokines and cytokine receptors in human microglia. J Neurosci Res 69:94–103

    Article  CAS  PubMed  Google Scholar 

  91. Thota C, Farmer T, Garfield RE, Menon R, Al-Hendy A (2012) Vitamin D elicits anti-inflammatory response, inhibits contractile-associated proteins, and modulates Toll-like receptors in human myometrial cells. Reprod Sci. https://doi.org/10.1177/1933719112459225

  92. Joshi S, Pantalena LC, Liu XK, Gaffen SL, Liu H, Rohowsky-Kochan C, Ichiyama K, Yoshimura A, Steinman L, Christakos S, Youssef S (2011) 1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol Cell Biol 31(17):3653–3669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Landel V, Annweiler C, Millet P, Morello M, Feron F (2016) Vitamin D, cognition and Alzheimer’s disease: the therapeutic benefit is in the D-tails. J Alzheimers Dis 53(2):419–444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Landel V, Millet P, Baranger K, Loriod B, Feron F (2016) Vitamin D interacts with Esr1 and Igf1 to regulate molecular pathways relevant to Alzheimer’s disease. Mol Neurodegener 11:22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Mizwicki MT, Liu G, Fiala M, Magpantay L, Sayre J, Siani A, Mahanian M, Weitzman R, Hayden EY, Rosenthal MJ, Nemere I, Ringman J, Teplow DB (2013) 1alpha,25-dihydroxyvitamin D3 and resolvin D1 retune the balance between amyloid-beta phagocytosis and inflammation in Alzheimer’s disease patients. J Alzheimers Dis 34(1):155–170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Briones TL, Darwish H (2012) Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden. J Neuroinflammation 9:244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Fernandez-Vizarra P, Fernandez AP, Castro-Blanco S, Encinas JM, Serrano J, Bentura ML, Munoz P, Martinez-Murillo R, Rodrigo J (2004) Expression of nitric oxide system in clinically evaluated cases of Alzheimer’s disease. Neurobiol Dis 15:287–305

    Article  CAS  PubMed  Google Scholar 

  98. Luth HJ, Munch G, Arendt T (2002) Aberrant expression of NOS isoforms in Alzheimer’s disease is structurally related to nitrotyrosine formation. Brain Res 953:135–143

    Article  PubMed  Google Scholar 

  99. Akama KT, Van Eldik LJ (2000) Beta-amyloid stimulation of inducible nitric-oxide synthase in astrocytes is interleukin-1beta- and tumor necrosis factor-alpha (TNFalpha)-dependent, and involves a TNFalpha receptor-associated factor- and NFkappaB-inducing kinase-dependent signaling mechanism. J Biol Chem 275(11):7918–7924

    Article  CAS  PubMed  Google Scholar 

  100. Garcion E, Nataf S, Berod A, Darcy F, Brachet P (1997) 1,25-Dihydroxyvitamin D3 inhibits the expression of inducible nitric oxide synthase in rat central nervous system during experimental allergic encephalomyelitis. Brain Res Mol Brain Res 45(2):255–267

    Article  CAS  PubMed  Google Scholar 

  101. Garcion E, Sindji L, Montero-Menei C, Andre C, Brachet P, Darcy F (1998) Expression of inducible nitric oxide synthase during rat brain inflammation: regulation by 1,25-dihydroxyvitamin D3. Glia 22(3):282–294

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The reviewed studies that are performed in Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine Department of Medical Biology, are financially supported by the Research Fund of Istanbul University (project nos. 21585, 26814, 26989, 30666, 51454, and 55157) and by the Scientific and Technological Research Council of Turkey-TUBITAK (project nos. 214S586, 214S585, 115S438, and 217S375).

Author information

Authors and Affiliations

  1. Brain and Neurodegenerative Disorders Research Laboratory, Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098, Istanbul, Turkey

    Erdinç Dursun & Duygu Gezen-Ak

Authors
  1. Erdinç Dursun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Duygu Gezen-Ak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erdinç Dursun.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dursun, E., Gezen-Ak, D. Vitamin D basis of Alzheimer’s disease: from genetics to biomarkers. Hormones 18, 7–15 (2019). https://doi.org/10.1007/s42000-018-0086-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42000-018-0086-5

Keywords

Search

Navigation