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Alkaline phosphatase: a potential biomarker for stroke and implications for treatment

  • Allison L. Brichacek
  • Candice M. Brown
Review Article
  • 106 Downloads

Abstract

Stroke is the fifth leading cause of death in the U.S., with more than 100,000 deaths annually. There are a multitude of risks associated with stroke, including aging, cardiovascular disease, hypertension, Alzheimer’s disease (AD), and immune suppression. One of the many challenges, which has so far proven to be unsuccessful, is the identification of a cost-effective diagnostic or prognostic biomarker for stroke. Alkaline phosphatase (AP), an enzyme first discovered in the 1920s, has been evaluated as a potential biomarker in many disorders, including many of the co-morbidities associated with stroke. This review will examine the basic biology of AP, and its most common isoenzyme, tissue nonspecific alkaline phosphatase (TNAP), with a specific focus on the central nervous system. It examines the preclinical and clinical evidence which supports a potential role for AP in stroke and suggests potential mechanism(s) of action for AP isoenzymes in stroke. Lastly, the review speculates on the clinical utility of AP isoenzymes as potential blood biomarkers for stroke or as AP-targeted treatments for stroke patients.

Keywords

Stroke Alkaline phosphatase Biomarker Tissue nonspecific alkaline phosphatase Blood-brain barrer 

Notes

Acknowledgements

The project was supported by NIH T32AG052375 (ALB) and K01NS081014, U54GM104942, P20 GM109098 (CMB). We appreciate insightful feedback from Ashley B. Petrone PhD.

References

  1. Adams HP, Brott TG, Furlan AJ, Gomez CR, Grotta J, Helgason CM, Kwiatkowski T, Lyden PD, Marler JR, Torner J, Feinberg W, Mayberg M, Thies W (1996) Guidelines for thrombolytic therapy for acute stroke: a supplement to the guidelines for the Management of Patients with acute ischemic stroke. Circulation 94:1167–1174.  https://doi.org/10.1161/01.CIR.94.5.1167 CrossRefPubMedGoogle Scholar
  2. Alam SN, Yammine H, Moaven O, Ahmed R, Moss AK, Biswas B, Muhammad N, Biswas R, Raychowdhury A, Kaliannan K, Ghosh S, Ray M, Hamarneh SR, Barua S, Malo NS, Bhan AK, Malo MS, Hodin RA (2014) Intestinal Alkaline Phosphatase Prevents Antibiotic-Induced Susceptibility to Enteric Pathogens. Annal Surg 259:715–722.  https://doi.org/10.1097/SLA.0b013e31828fae14 CrossRefGoogle Scholar
  3. Anstrom JA, Brown WR, Moody DM, Thore CR, Challa VR, Block SM (2002) Temporal expression pattern of cerebrovascular endothelial cell alkaline phosphatase during human gestation. J Neuropathol Exp Neurol 61:76–84CrossRefGoogle Scholar
  4. Arun P, Oguntayo S, Albert SV, Gist I, Wang Y, Nambiar MP, Long JB (2015) Acute decrease in alkaline phosphatase after brain injury: a potential mechanism for tauopathy. Neurosci Lett 609:152–158.  https://doi.org/10.1016/j.neulet.2015.10.036 CrossRefPubMedGoogle Scholar
  5. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967.  https://doi.org/10.1126/science.275.5302.964 CrossRefPubMedGoogle Scholar
  6. Balasubramaniam S, Bowling F, Carpenter K, Earl J, Chaitow J, Pitt J, Mornet E, Sillence D, Ellaway C (2010) Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy with abnormal neurotransmitter metabolism secondary to reduced co-factor pyridoxal-5′-phosphate availability. J Inherit Metab Dis 33:25–33.  https://doi.org/10.1007/s10545-009-9012-y CrossRefGoogle Scholar
  7. Bannister RG, Romanul FCA (1963) The localization of alkaline phosphatase activity in cerebral blood vessels. J Neurol Neurosurg Psychiatry 26:333–340.  https://doi.org/10.1136/jnnp.26.4.333 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Barnadas A, Manso L, de la Piedra C, Meseguer C, Crespo C, Gómez P, Calvo L, Martinez P, Ruiz-Borrego M, Perelló A, Antón A, Codes M, Margelí M, Murias A, Salvador J, Seguí MÁ, de Juan A, Gavilá J, Luque M, Pérez D, Zamora P, Arizcuma A, Chacón JI, Heras L, Martin-Fernández M, Mahillo-Fernández I, Tusquets I (2014) Bone turnover markers as predictive indicators of outcome in patients with breast cancer and bone metastases treated with bisphosphonates: results from a 2-year multicentre observational study (ZOMAR study). Bone 68:32–40.  https://doi.org/10.1016/j.bone.2014.07.036 CrossRefPubMedGoogle Scholar
  9. Barvencik F, Beil FT, Gebauer M, Busse B, Koehne T, Seitz S, Zustin J, Pogoda P, Schinke T, Amling M (2011) Skeletal mineralization defects in adult hypophosphatasia—a clinical and histological analysis. Osteoporos Int 22:2667–2675.  https://doi.org/10.1007/s00198-011-1528-y CrossRefPubMedGoogle Scholar
  10. Beghetti M, Rimensberger PC, Kalangos A, Habre W, Gervaix A (2003) Kinetics of procalcitonin, interleukin 6 and C-reactive protein after cardiopulmonary-bypass in children. Cardiol Young 13:161–167CrossRefGoogle Scholar
  11. Bell MA, Ball MJ (1985) Laminar variation in the microvascular architecture of normal human visual cortex (area 17). Brain Res 335:139–143.  https://doi.org/10.1016/0006-8993(85)90284-7 CrossRefPubMedGoogle Scholar
  12. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O'Flaherty M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, Ritchey MD, Rodriguez CJ, Roth GA, Rosamond WD, Sampson UKA, Satou GM, Shah SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee (2018) Heart disease and stroke statistics 2018 update: a report from the American Heart Association. Circulation 137:e67–e492.  https://doi.org/10.1161/cir.0000000000000558 CrossRefPubMedGoogle Scholar
  13. Bentala H, Verweij WR, der Vlag AH-V et al (2002) Removal of Phosphate from Lipid A as a Strategy to Detoxify Lipopolysaccharide. Shock 18:561–566.  https://doi.org/10.1097/00024382-200212000-00013 CrossRefPubMedGoogle Scholar
  14. Berer K, Mues M, Koutrolos M, Rasbi ZA, Boziki M, Johner C, Wekerle H, Krishnamoorthy G (2011) Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479:538–541.  https://doi.org/10.1038/nature10554 CrossRefGoogle Scholar
  15. Berger J, Garattini E, Hua JC, Udenfriend S (1987) Cloning and sequencing of human intestinal alkaline phosphatase cDNA. Proc Natl Acad Sci 84:695–698.  https://doi.org/10.1073/pnas.84.3.695 CrossRefPubMedGoogle Scholar
  16. Beumer C (2003) Calf intestinal alkaline phosphatase, a novel therapeutic drug for lipopolysaccharide (LPS)-mediated diseases, attenuates LPS toxicity in mice and piglets. J Pharmacol Exp Ther 307:737–744.  https://doi.org/10.1124/jpet.103.056606 CrossRefPubMedGoogle Scholar
  17. Bonaventura A, Liberale L, Vecchie A et al (2016) Update on inflammatory biomarkers and treatments in ischemic stroke. Int J Mol Sci 17.  https://doi.org/10.3390/ijms17121967 CrossRefGoogle Scholar
  18. Brown WR, Moody DM, Challa VR, Thore CR, Anstrom JA (2002) Venous collagenosis and arteriolar tortuosity in leukoaraiosis. J Neurol Sci 203:159–163.  https://doi.org/10.1016/s0022-510x(02)00283-6 CrossRefPubMedGoogle Scholar
  19. Brun-Heath I, Ermonval M, Chabrol E, Xiao J, Palkovits M, Lyck R, Miller F, Couraud PO, Mornet E, Fonta C (2011) Differential expression of the bone and the liver tissue non-specific alkaline phosphatase isoforms in brain tissues. Cell Tissue Res 343:521–536.  https://doi.org/10.1007/s00441-010-1111-4 CrossRefPubMedGoogle Scholar
  20. Bruno A, Shah N, Akinwuntan AE, Close B, Switzer JA (2013) Stroke size correlates with functional outcome on the simplified modified Rankin scale questionnaire. J Stroke Cerebrovasc Dis 22:781–783.  https://doi.org/10.1016/j.jstrokecerebrovasdis.2012.03.011 CrossRefPubMedGoogle Scholar
  21. Buchet R, Millán JL, Magne D (2013) Multisystemic Functions of Alkaline Phosphatases. In: Millán J (ed) Phosphatase Modulators. Methods in Molecular Biology (Methods and Protocols). Humana Press, TotowaGoogle Scholar
  22. Buljevac D, Flach HZ, Hop WCJ, Hijdra D, Laman JD, Savelkoul HFJ, van der Meché FGA, van Doorn PA, Hintzen RQ (2002) Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain 125:952–960.  https://doi.org/10.1093/brain/awf098 CrossRefPubMedGoogle Scholar
  23. Bushnell CD, Hurn P, Colton C, Miller VM, del Zoppo G, Elkind MSV, Stern B, Herrington D, Ford-Lynch G, Gorelick P, James A, Brown CM, Choi E, Bray P, Newby LK, Goldstein LB, Simpkins J (2006) Advancing the study of stroke in women: summary and recommendations for future research from an NINDS-sponsored multidisciplinary working group. Stroke 37:2387–2399.  https://doi.org/10.1161/01.STR.0000236053.37695.15 CrossRefPubMedGoogle Scholar
  24. Calhau C, Martel F, Pinheiro-Silva S, Pinheiro H, Soares-da-Silva P, Hipólito-Reis C, Azevedo I (2002) Modulation of insulin transport in rat brain microvessel endothelial cells by an ecto-phosphatase activity. J Cell Biochem 84:389–400.  https://doi.org/10.1002/jcb.10027 CrossRefPubMedGoogle Scholar
  25. Champion EE, Glazier JD, Greenwood SL, et al (2003) Localization of alkaline phosphatase and Ca2+-ATPase in the cat placenta. Placenta 24:453–461.  https://doi.org/10.1053/plac.2002.0952 CrossRefGoogle Scholar
  26. Charegaonkar PM, Rindani TH (1961) Effect of age, sex and gonadal hormone on alkaline phosphatase activity of rat brain tissue. P Indian Acad Sci B 54:113–116Google Scholar
  27. Chen KT, Malo MS, Moss AK, Zeller S, Johnson P, Ebrahimi F, Mostafa G, Alam SN, Ramasamy S, Warren HS, Hohmann EL, Hodin RA (2010) Identification of specific targets for the gut mucosal defense factor intestinal alkaline phosphatase. Am J Physiol Gastrointest Liver Physiol 299:G467–G475.  https://doi.org/10.1152/ajpgi.00364.2009 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Cheung BM, Ong KL, Cheung RV et al (2008) Association between plasma alkaline phosphatase and C-reactive protein in Hong Kong Chinese. Clin Chem Lab Med 46:523–527.  https://doi.org/10.1515/cclm.2008.111 CrossRefPubMedGoogle Scholar
  29. Choi J, Pai SH (2000) Serum lipid concentrations change with serum alkaline phosphatase activity during pregnancy. Ann Clin Lab Sci 30:422–428PubMedGoogle Scholar
  30. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752–758.  https://doi.org/10.1038/nn1472 CrossRefPubMedGoogle Scholar
  31. Davidson J, Tong S, Hauck A, Lawson D, Jaggers J, Kaufman J, da Cruz E (2012) Alkaline phosphatase activity after cardiothoracic surgery in infants and correlation with post-operative support and inflammation: a prospective cohort study. Crit Care 16:R160.  https://doi.org/10.1186/cc11483 CrossRefPubMedPubMedCentralGoogle Scholar
  32. de Vries EMG, Wang J, Leeflang MMG, Boonstra K, Weersma RK, Beuers UH, Geskus RB, Ponsioen CY (2016) Alkaline phosphatase at diagnosis of primary sclerosing cholangitis and 1 year later: evaluation of prognostic value. Liver Int 36:1867–1875.  https://doi.org/10.1111/liv.13110 CrossRefPubMedGoogle Scholar
  33. Deracinois B, Duban-Deweer S, Pottiez G, Cecchelli R, Karamanos Y, Flahaut C (2012) TNAP and EHD1 are over-expressed in bovine brain capillary endothelial cells after the re-induction of blood-brain barrier properties. PLoS One 7:e48428.  https://doi.org/10.1371/journal.pone.0048428 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Deracinois B, Lenfant A-M, Dehouck M-P, Flahaut C (2015) Tissue non-specific alkaline phosphatase (TNAP) in vessels of the brain. In: Fonta C, Négyessy L (eds) Neuronal tissue-nonspecific alkaline phosphatase (TNAP). Springer Netherlands, Dordrecht, pp 125–151CrossRefGoogle Scholar
  35. Dhanda S, Gupta S, Halder A, Sunkaria A, Sandhir R (2018) Systemic inflammation without gliosis mediates cognitive deficits through impaired BDNF expression in bile duct ligation model of hepatic encephalopathy. Brain Behav Immun 70:214–232.  https://doi.org/10.1016/j.bbi.2018.03.002 CrossRefPubMedGoogle Scholar
  36. Dirnagl U, Endres M (2014) Found in translation: preclinical stroke research predicts human pathophysiology, clinical phenotypes, and therapeutic outcomes. Stroke 45(5):1510–1518.  https://doi.org/10.1161/strokeaha.113.004075 CrossRefPubMedGoogle Scholar
  37. Dirnagl U, Iadecola C, Moskowitz M (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397CrossRefGoogle Scholar
  38. Ebrahimi F, Malo MS, Alam SN, Moss AK, Yammine H, Ramasamy S, Biswas B, Chen KT, Muhammad N, Mostafa G, Warren HS, Hohmann EL, Hodin RA (2011) Local peritoneal irrigation with intestinal alkaline phosphatase is protective against peritonitis in mice. J Gastrointest Surg 15:860–869.  https://doi.org/10.1007/s11605-010-1405-6 CrossRefPubMedGoogle Scholar
  39. Ebuehi OAT, Asonye CL (2007) Gender and alcohol consumption affect human serum enzymes, protein and bilirubin. Asian J Biochem 2:330–336CrossRefGoogle Scholar
  40. El Hafny B, Bourre J-M, Roux F (1996) Synergistic stimulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities by retinoic acid and astroglial factors in immortalized rat brain microvessel endothelial cells. J Cell Physiol 167:451–460.  https://doi.org/10.1002/(SICI)1097-4652(199606)167:3<451::AID-JCP9>3.0.CO;2-O
  41. Ermonval M, Baudry A, Baychelier F, Pradines E, Pietri M, Oda K, Schneider B, Mouillet-Richard S, Launay JM, Kellermann O (2009) The cellular prion protein interacts with the tissue non-specific alkaline phosphatase in membrane microdomains of Bioaminergic neuronal cells. PLoS One 4:e6497.  https://doi.org/10.1371/journal.pone.0006497 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Fenuku RI, Foli AK (1975) Variations in total serum alkaline phosphatase activity with age and sex in adult and adolescent Ghanaians. Clin Chim Acta 60:303–306CrossRefGoogle Scholar
  43. Fonta C (2004) Areal and subcellular localization of the ubiquitous alkaline phosphatase in the primate cerebral cortex: evidence for a role in neurotransmission. Cereb Cortex 14:595–609.  https://doi.org/10.1093/cercor/bhh021 CrossRefPubMedGoogle Scholar
  44. Fonta C, Imbert M (2002) Vascularization in the primate visual cortex during development. Cereb Cortex 12:199–211CrossRefGoogle Scholar
  45. Fonta C, Negyessy L, Renaud L, Barone P (2005) Postnatal development of alkaline phosphatase activity correlates with the maturation of neurotransmission in the cerebral cortex. J Comp Neurol 486:179–196.  https://doi.org/10.1002/cne.20524 CrossRefPubMedGoogle Scholar
  46. Friede RL (1966) A quantitative mapping of alkaline phosphatase in the brain of the rhesus monkey. J Neurochem 13:197–203CrossRefGoogle Scholar
  47. Gandolfi M, Smania N, Vella A, et al (2017) Assessed and Emerging Biomarkers in Stroke and Training-Mediated Stroke Recovery: State of the Art. Neural Plasticity 2017:15 pages.  https://doi.org/10.1155/2017/1389475 CrossRefGoogle Scholar
  48. Gdara NB, Belgacem A, Khemiri I, Mannai S, Bitri L (2018) Protective effects of phycocyanin on ischemia/reperfusion liver injuries. Biomed Pharmacother 102:196–202.  https://doi.org/10.1016/j.biopha.2018.03.025 CrossRefPubMedGoogle Scholar
  49. Giessen C, Nagel D, Glas M, Spelsberg F, Lau-Werner U, Modest DP, Michl M, Heinemann V, Stieber P, Schulz C (2014) Evaluation of preoperative serum markers for individual patient prognosis in stage I–III rectal cancer. Tumor Biol 35:10237–10248.  https://doi.org/10.1007/s13277-014-2338-6 CrossRefGoogle Scholar
  50. Golik A, Rubio A, Weintraub M, Byrne L (1991) Elevated serum liver enzymes in obesity: a dilemma during clinical trials. Int J Obes 15:797–801PubMedGoogle Scholar
  51. Gong C-X, Singh TJ, Grundke-Iqbal I, Iqbal K (1993) Phosphoprotein phosphatase activities in Alzheimer disease brain. J Neurochem 61:921–927.  https://doi.org/10.1111/j.1471-4159.1993.tb03603.x CrossRefPubMedGoogle Scholar
  52. Hammerich KH, Donahue TF, Rosner IL, Cullen J, Kuo HC, Hurwitz L, Chen Y, Bernstein M, Coleman J, Danila DC, Metwalli AR (2017) Alkaline phosphatase velocity predicts overall survival and bone metastasis in patients with castration-resistant prostate cancer. Urol Oncol-Semin Ori 35:460.e21–460.e28.  https://doi.org/10.1016/j.urolonc.2017.02.001 CrossRefGoogle Scholar
  53. Hanics J, Janos B, Xiao J et al (2012) Ablation of TNAP function compromises myelination and synaptogenesis in the mouse brain. Cell Tissue Res 349:459–471.  https://doi.org/10.1007/s00441-012-1455-z CrossRefPubMedPubMedCentralGoogle Scholar
  54. Hanna AN, Waldman WJ, Lott JA et al (1997) Increased alkaline phosphatase isoforms in autoimmune diseases. Clin Chem 43:1357–1364PubMedGoogle Scholar
  55. Harris H (1990) The human alkaline phosphatases: what we know and what we don’t know. Clin Chim Acta 186:133–150.  https://doi.org/10.1016/0009-8981(90)90031-M CrossRefPubMedGoogle Scholar
  56. Heemskerk S, Masereeuw R, Moesker O, Bouw MP, van der Hoeven J, Peters WH, Russel FG, Pickkers P, APSEP Study Group (2009) Alkaline phosphatase treatment improves renal function in severe sepsis or septic shock patients. Crit Care Med 32:417–423.  https://doi.org/10.1097/CCM.0b013e31819598af CrossRefGoogle Scholar
  57. Heinzerling NP, Liedel JL, Welak SR, Fredrich K, Biesterveld BE, Pritchard KA Jr, Gourlay DM (2014) Intestinal alkaline phosphatase is protective to the preterm rat pup intestine. J Pediatr Surg 49:954–960.  https://doi.org/10.1016/j.jpedsurg.2014.01.031 CrossRefPubMedPubMedCentralGoogle Scholar
  58. Herbeth B, Bagrel A, Dalo B, Siest G, Leclerc J, Rauber G (1981) Influence of oral contraceptives of differing dosages on α-1-antitrypsin, γ-glutamyltransferase and alkaline phosphatase. Clin Chim Acta 112:293–299.  https://doi.org/10.1016/0009-8981(81)90452-6 CrossRefPubMedGoogle Scholar
  59. Huizinga R, Kreft KL, Onderwater S, Boonstra JG, Brands R, Hintzen RQ, Laman JD (2012) Endotoxin- and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation. J Neuroinflammation 9:266–266.  https://doi.org/10.1186/1742-2094-9-266 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Iadecola C, Nedergaard M (2007) Glial regulation of the cerebral microvasculature. Nat Neurosci 10:1369–1376.  https://doi.org/10.1038/nn2003 CrossRefPubMedGoogle Scholar
  61. Jassam NJ, Horner J, Marzo-Ortega H et al (2009) Transient rise in alkaline phosphatase activity in adults. BMJ case reports 2009:bcr0920092250–bcr0920092250.  https://doi.org/10.1136/bcr.09.2009.2250 Google Scholar
  62. Jiang X, Andjelkovic AV, Zhu L, Yang T, Bennett MVL, Chen J, Keep RF, Shi Y (2018) Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog Neurobiol 163–164:144–171.  https://doi.org/10.1016/j.pneurobio.2017.10.001 CrossRefPubMedGoogle Scholar
  63. Jickling GC, Sharp FR (2015) Improving the translation of animal ischemic stroke studies to humans. Metab Brain Dis 30:461–467.  https://doi.org/10.1007/s11011-014-9499-2 CrossRefPubMedGoogle Scholar
  64. Kaliannan K, Hamarneh SR, Economopoulos KP, Nasrin Alam S, Moaven O, Patel P, Malo NS, Ray M, Abtahi SM, Muhammad N, Raychowdhury A, Teshager A, Mohamed MMR, Moss AK, Ahmed R, Hakimian S, Narisawa S, Millan JL, Hohmann E, Warren HS, Bhan AK, Malo MS, Hodin RA (2013) Intestinal alkaline phosphatase prevents metabolic syndrome in mice. Proc Natl Acad Sci 110:7003–7008.  https://doi.org/10.1073/pnas.1220180110 CrossRefPubMedGoogle Scholar
  65. Kang YH, West WL (1982) Ultrastructural localization of glucose-6-phosphatase and alkaline phosphatase in the vaginal epithelium of rat. J Morphol 171:1–10.  https://doi.org/10.1002/jmor.1051710102 CrossRefPubMedGoogle Scholar
  66. Karabulut A, Sahin I, Avci II, Okuyan E, Dogan Z, Uzunlar B, Satilmis S (2014) Impact of serum alkaline phosphatase level on coronary collateral circulation. Kardiol Pol 72:1388–1393.  https://doi.org/10.5603/KP.a2014.0114 CrossRefPubMedGoogle Scholar
  67. Kellett KAB, Williams J, Vardy ERLC, Smith AD, Hooper NM (2011) Plasma alkaline phosphatase is elevated in Alzheimer’s disease and inversely correlates with cognitive function. Int J Mol Epidemiol Genet 2:114–121Google Scholar
  68. Kelly PJ, Jowsey J, Riggs BL, Elveback LR (1967) Relationship between serum phosphate concentration and bone resorption in osteoporosis. J Lab Clin Med 69:110–115PubMedGoogle Scholar
  69. Khan MJ, Ahmed B, Ahmed S, Khan M (2016) Increase in serum alkaline phosphatase due to fatty meal in undergraduate students of Khyber Medical University, Khyber Pakhtunkhwa. J Pak Med Assoc 66:378–379PubMedGoogle Scholar
  70. Khoshnam SE, Winlow W, Farbood Y, Moghaddam HF, Farzaneh M (2017) Emerging roles of microRNAs in ischemic stroke: as possible therapeutic agents. J Stroke 19:166–187.  https://doi.org/10.5853/jos.2016.01368 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Kiffer-Moreira T, Sheen CR, Gasque KC da S et al (2014) Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential. PLoS One 9:e89374.  https://doi.org/10.1371/journal.pone.0089374 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Kim J, Song T-J, Song D et al (2013) Serum alkaline phosphatase and phosphate in cerebral atherosclerosis and functional outcomes after cerebral infarction. Stroke 44:3547–3549.  https://doi.org/10.1161/strokeaha.113.002959 CrossRefPubMedGoogle Scholar
  73. Kim GS, Im E, Rhee JH (2017) Association of physical activity on body composition, cardiometabolic risk factors, and prevalence of cardiovascular disease in the Korean population (from the fifth Korea national health and nutrition examination survey, 2008-2011). BMC Public Health 17:275.  https://doi.org/10.1186/s12889-017-4126-x CrossRefPubMedPubMedCentralGoogle Scholar
  74. Koyama I, Matsunaga T, Harada T, Hokari S, Komoda T (2002) Alkaline phosphatases reduce toxicity of lipopolysaccharides in vivo and in vitro through dephosphorylation. Clin Biochem 35:455–461.  https://doi.org/10.1016/S0009-9120(02)00330-2 CrossRefPubMedGoogle Scholar
  75. Koyama T, Taka A, Togashi H (2006) Cardiovascular effects produced by a traditional fungal medicine, Fuscoporia obliqua extract, and microvessels in the left ventricular wall of stroke-prone spontaneously hypertensive rat (SHRSP). Clin Hemorheol Microcirc 35:491–498PubMedGoogle Scholar
  76. Kunjappu JJ, Mathew VB, Hegde S et al (2012) Assessment of the alkaline phosphatase level in gingival crevicular fluid, as a biomarker to evaluate the effect of scaling and root planing on chronic periodontitis: an in vivo study. J. Oral Maxillofac. Pathol. 16:54–57.  https://doi.org/10.4103/0973-029x.92974 CrossRefGoogle Scholar
  77. Kunutsor SK, Apekey TA, Khan H (2014) Liver enzymes and risk of cardiovascular disease in the general population: a meta-analysis of prospective cohort studies. Atherosclerosis 236:7–17.  https://doi.org/10.1016/j.atherosclerosis.2014.06.006 CrossRefPubMedGoogle Scholar
  78. Lampl Y, Paniri Y, Eshel Y, Sarova-Pincha I (1990) Alkaline phosphatase level in CSF in various brain tumors and pulmonary carcinomatous meningitis. J Neuro-Oncol 9:35–40.  https://doi.org/10.1007/bf00167066 CrossRefGoogle Scholar
  79. Langer D, Hammer K, Koszalka P et al (2008) Distribution of ectonucleotidases in the rodent brain revisited. Cell Tissue Res 334:199–217.  https://doi.org/10.1007/s00441-008-0681-x CrossRefPubMedGoogle Scholar
  80. Langhorne P, Stott DJ, Robertson L, MacDonald J, Jones L, McAlpine C, Dick F, Taylor GS, Murray G (2000) Medical complications after stroke : a multicenter study. Stroke 31:1223–1229.  https://doi.org/10.1161/01.STR.31.6.1223 CrossRefPubMedGoogle Scholar
  81. Lee H-B, Kim J, Kim S-H, Kim S, Kim OJ, Oh SH (2015) Association between serum alkaline phosphatase level and cerebral small vessel disease. PLoS One 10:e0143355.  https://doi.org/10.1371/journal.pone.0143355 CrossRefPubMedPubMedCentralGoogle Scholar
  82. Lester E (1977) Serum enzyme levels in healthy old people. Ann. Clin. Biochem.14:118–119.  https://doi.org/10.1177/000456327701400121 CrossRefGoogle Scholar
  83. Li X, Wang D, Yang C, Zhou Q, Zhuoga SL, Wang LQ, Yao HX, Zhang Q, Ai Q, Yang CX, Xu JC (2018) Establishment of age- and gender-specific pediatric reference intervals for liver function tests in healthy Han children. World J Pediatr 14:151–159.  https://doi.org/10.1007/s12519-018-0126-x CrossRefPubMedPubMedCentralGoogle Scholar
  84. Liu J, Wang D, Li J, Xiong Y, Liu B, Wei C, Wu S, Liu M (2016) High serum alkaline phosphatase levels in relation to multi-cerebral microbleeds in acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease. Curr Neurovasc Res 13:303–308.  https://doi.org/10.2174/1567202613666160817095623 CrossRefPubMedGoogle Scholar
  85. Low MG (1987) Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors. Biochem J 244:1–13.  https://doi.org/10.1042/bj2440001 CrossRefPubMedPubMedCentralGoogle Scholar
  86. Low MG, Zilversmit DB (1980) Role of phosphatidylinositol in attachment of alkaline phosphatase to membranes. Biochemistry 19:3913–3918.  https://doi.org/10.1021/bi00558a004 CrossRefPubMedGoogle Scholar
  87. Lukas M, Drastich P, Konecny M et al (2010) Exogenous alkaline phosphatase for the treatment of patients with moderate to severe ulcerative colitis. Inflamm Bowel Dis 16:1180–1186.  https://doi.org/10.1002/ibd.21161 CrossRefPubMedGoogle Scholar
  88. Luo Y, Li J, Zhang J, Xu Y (2013) Elevated bilirubin after acute ischemic stroke linked to the stroke severity. Int J Dev Neurosci 31:634–638.  https://doi.org/10.1016/j.ijdevneu.2013.08.002 CrossRefPubMedGoogle Scholar
  89. MacGregor GR, Zambrowicz BP, Soriano P (1995) Tissue non-specific alkaline phosphatase is expressed in both embryonic and extraembryonic lineages during mouse embryogenesis but is not required for migration of primordial germ cells. Development 121:1487–1496PubMedGoogle Scholar
  90. Magnusson P, Häger A, Larsson L (1995) Serum osteocalcin and bone and liver alkaline phosphatase isoforms in healthy children and adolescents. Pediatr Res 38:955–961.  https://doi.org/10.1203/00006450-199512000-00021 CrossRefPubMedGoogle Scholar
  91. Makil ES, Tang X, Frazier EA, Collins RT 2nd (2017) Alkaline phosphatase: a biomarker of cardiac function in pediatric patients. Pediatr Cardiol 38:762–769.  https://doi.org/10.1007/s00246-017-1577-x CrossRefGoogle Scholar
  92. Malo MS, Alam SN, Mostafa G, Zeller SJ, Johnson PV, Mohammad N, Chen KT, Moss AK, Ramasamy S, Faruqui A, Hodin S, Malo PS, Ebrahimi F, Biswas B, Narisawa S, Millan JL, Warren HS, Kaplan JB, Kitts CL, Hohmann EL, Hodin RA (2010) Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota. Gut 59:1476–1484.  https://doi.org/10.1136/gut.2010.211706 CrossRefPubMedGoogle Scholar
  93. Martinez B, Peplow PV (2016) Blood microRNAs as potential diagnostic and prognostic markers in cerebral ischemic injury. Neural Regen Res 11:1375–1378.  https://doi.org/10.4103/1673-5374.191196 CrossRefPubMedPubMedCentralGoogle Scholar
  94. Martínez-Moya P, Ortega-González M, González R, Anzola A, Ocón B, Hernández-Chirlaque C, López-Posadas R, Suárez MD, Zarzuelo A, Martínez-Augustin O, Sánchez de Medina F (2012) Exogenous alkaline phosphatase treatment complements endogenous enzyme protection in colonic inflammation and reduces bacterial translocation in rats. Pharmacol Res 66:144–153.  https://doi.org/10.1016/j.phrs.2012.04.006 CrossRefPubMedGoogle Scholar
  95. Matute C, Torre I, Pérez-Cerdá F et al (2007) P2X7 receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis. J Neurosci 27:9525–9533.  https://doi.org/10.1523/jneurosci.0579-07.2007 CrossRefPubMedGoogle Scholar
  96. Mayo Clinic Test ID (2017) ALKI Alkaline Phosphatase. Total and Isoenzymes, SerumGoogle Scholar
  97. Menahan LA, Sobocinski KA, Austin BP (1985) Characterization of elevated plasma alkaline phosphatase activity in genetically obese mice. Metab Clin Exp 34:272–277.  https://doi.org/10.1016/0026-0495(85)90012-5 CrossRefPubMedGoogle Scholar
  98. Metwalli AR, Rosner IL, Cullen J, Chen Y, Brand T, Brassell SA, Lesperance J, Porter C, Sterbis J, McLeod DG (2014) Elevated alkaline phosphatase velocity strongly predicts overall survival and the risk of bone metastases in castrate-resistant prostate cancer. Urol Oncol-Semin Ori  32:761–768.  https://doi.org/10.1016/j.urolonc.2014.03.024 CrossRefGoogle Scholar
  99. Meyer P (1963) Histochemistry of the developing human brain I. Alkaline phosphatase, acid phosphatase, and AS esterase in the cerebellum. Acta Neurol Scand 39:123–138.  https://doi.org/10.1111/j.1600-0404.1963.tb05314.x CrossRefGoogle Scholar
  100. Meythaler JM, Hazlewood J, DeVivo MJ, Rosner M (1998) Elevated liver enzymes after nontraumatic intracranial hemorrhages. Arch Phys Med Rehabil 79:766–771.  https://doi.org/10.1016/s0003-9993(98)90354-9 CrossRefPubMedGoogle Scholar
  101. Millan JL (1986) Molecular cloning and sequence analysis of human placental alkaline phosphatase. J Biol Chem 261:3112–3115PubMedGoogle Scholar
  102. Millan JL, Manes T (1988) Seminoma-derived Nagao isozyme is encoded by a germ-cell alkaline phosphatase gene. Proc Natl Acad Sci 85:3024–3028.  https://doi.org/10.1073/pnas.85.9.3024 CrossRefPubMedGoogle Scholar
  103. Molla A, Lalani R, Khurshid M et al (1990) Serum alkaline phosphatase in apparently healthy Karachi population. J Pak Med Assoc:182–184Google Scholar
  104. Moore CA, Ward JC, Rivas ML, Magill HL, Whyte MP (1990) Infantile hypophosphatasia: autosomal recessive transmission to two related sibships. Am J Med Genet 36:15–22.  https://doi.org/10.1002/ajmg.1320360105 CrossRefPubMedGoogle Scholar
  105. Mori S, Nagano M (1985) Electron-microscopic cytochemistry of alkaline-phosphatase activity in endothelium, pericytes and oligodendrocytes in the rat brain. Histochemistry 82:225–231.  https://doi.org/10.1007/BF00501399 CrossRefPubMedGoogle Scholar
  106. Moss DW (1982) Alkaline phosphatase isoenzymes. Clin Chem 28:2007–2016PubMedGoogle Scholar
  107. Muscari A, Collini A, Fabbri E, Giovagnoli M, Napoli C, Rossi V, Vizioli L, Bonfiglioli A, Magalotti D, Puddu GM, Zoli M (2014) Changes of liver enzymes and bilirubin during ischemic stroke: mechanisms and possible significance. BMC Neurol 14.  https://doi.org/10.1186/1471-2377-14-122
  108. Naik RB, Gosling P, Price CP (1977) Comparative study of alkaline phosphatase isoenzymes, bone histology, and skeletal radiography in dialysis bone disease. Br Med J 1:1307–1310CrossRefGoogle Scholar
  109. Namba S, Yamaoka-Tojo M, Kakizaki R, Nemoto T, Fujiyoshi K, Hashikata T, Kitasato L, Hashimoto T, Kameda R, Meguro K, Shimohama T, Tojo T, Ako J (2017) Effects on bone metabolism markers and arterial stiffness by switching to rivaroxaban from warfarin in patients with atrial fibrillation. Heart Vessel 32:977–982.  https://doi.org/10.1007/s00380-017-0950-2 CrossRefGoogle Scholar
  110. Narisawa S, Hasegawa H, Watanabe K, Millán JL (1994) Stage-specific expression of alkaline phosphatase during neural development in the mouse. Dev Dyn 201:227–235.  https://doi.org/10.1002/aja.1002010306 CrossRefPubMedGoogle Scholar
  111. Ndrepepa G, Xhepa E, Braun S, Cassese S, Fusaro M, Schunkert H, Kastrati A (2017) Alkaline phosphatase and prognosis in patients with coronary artery disease. Eur J Clin Investig 47:378–387.  https://doi.org/10.1111/eci.12752 CrossRefGoogle Scholar
  112. Nishihara Y, Hayashi Y, Fujii T, Adachi T, Stigbrand T, Hirano K (1994) The alkaline phosphatase in human plexus chorioideus. Biochim Biophys Acta Protein Struct Mol Enzymol 1209:274–278.  https://doi.org/10.1016/0167-4838(94)90196-1 CrossRefGoogle Scholar
  113. Nogai A, Siffrin V, Bonhagen K, Pfueller CF, Hohnstein T, Volkmer-Engert R, Bruck W, Stadelmann C, Kamradt T (2005) Lipopolysaccharide injection induces relapses of experimental autoimmune encephalomyelitis in nontransgenic mice via bystander activation of autoreactive CD4+ cells. J Immunol 175:959–966.  https://doi.org/10.4049/jimmunol.175.2.959 CrossRefPubMedGoogle Scholar
  114. Nowak LG, Rosay B, Czege D, Fonta C (2015) Tetramisole and levamisole suppress neuronal activity independently from their inhibitory action on tissue non-specific alkaline phosphatase in mouse cortex. In: Fonta C, Negyessy L (eds) Neuronal tissue-nonspecific alkaline phosphatase (TNAP). Springer Netherlands, Dordrecht, pp 239–281CrossRefGoogle Scholar
  115. Okesina AB, Donaldson D, Lascelles PT, Morris P (1995) Effect of gestational age on levels of serum alkaline phosphatase isoenzymes in healthy pregnant women. Int J Gynecol Obstet 48:25–29.  https://doi.org/10.1016/0020-7292(94)02248-8 CrossRefGoogle Scholar
  116. Paiva J, Damjanov I, Lange PH, Harris H (1983) ImmunohistochemicaI localization of placental-like AIkaline phosphatase in testis and germ-cell tumors using monoclonal antibodies. Am J Pathol 111:156–165PubMedPubMedCentralGoogle Scholar
  117. Paritpokee N, Tangkijvanich P, Teerasaksilp S, Wiwanitkit V, Lertmaharit S, Tosukhowong P (1999) Fast liver alkaline phosphatase isoenzyme in diagnosis of malignant biliary obstruction. J Med Assoc Thail 82:1241–1246Google Scholar
  118. Park J-B, Kang D, Yang H-M, Cho HJ, Park KW, Lee HY, Kang HJ, Koo BK, Kim HS (2013) Serum alkaline phosphatase is a predictor of mortality, myocardial infarction, or stent thrombosis after implantation of coronary drug-eluting stent. Eur Heart J 34:920–931.  https://doi.org/10.1093/eurheartj/ehs419 CrossRefPubMedGoogle Scholar
  119. Peters E, Masereeuw R, Pickkers P (2014) The potential of alkaline phosphatase as a treatment for sepsis-associated acute kidney injury. Nephron Clin Pract 127:144–148.  https://doi.org/10.1159/000363256 CrossRefGoogle Scholar
  120. Peters E, Geraci S, Heemskerk S, Wilmer MJ, Bilos A, Kraenzlin B, Gretz N, Pickkers P, Masereeuw R (2015) Alkaline phosphatase protects against renal inflammation through dephosphorylation of lipopolysaccharide and adenosine triphosphate. Br J Pharmacol 172:4932–4945.  https://doi.org/10.1111/bph.13261 CrossRefPubMedPubMedCentralGoogle Scholar
  121. Peters E, Ergin B, Kandil A, Gurel-Gurevin E, van Elsas A, Masereeuw R, Pickkers P, Ince C (2016a) Effects of a human recombinant alkaline phosphatase on renal hemodynamics, oxygenation and inflammation in two models of acute kidney injury. Toxicol Appl Pharmacol 313:88–96.  https://doi.org/10.1016/j.taap.2016.10.015 CrossRefPubMedGoogle Scholar
  122. Peters E, Heuberger JAAC, Tiessen R, van Elsas A, Masereeuw R, Arend J, Stevens J, Pickkers P (2016b) Pharmacokinetic modeling and dose selection in a randomized, double-blind, placebo-controlled trial of a human recombinant alkaline phosphatase in healthy volunteers. Clin Pharmacokinet 55:1227–1237.  https://doi.org/10.1007/s40262-016-0399-y CrossRefPubMedPubMedCentralGoogle Scholar
  123. Peters E, Schirris T, van Asbeck AH, Gerretsen J, Eymael J, Ashikov A, Adjobo-Hermans MJW, Russel F, Pickkers P, Masereeuw R (2017) Effects of a human recombinant alkaline phosphatase during impaired mitochondrial function in human renal proximal tubule epithelial cells. Eur J Pharmacol 796:149–157.  https://doi.org/10.1016/j.ejphar.2016.12.034 CrossRefPubMedGoogle Scholar
  124. Pickkers P, Snellen F, Rogiers P, Bakker J, Jorens P, Meulenbelt J, Spapen H, Tulleken JE, Lins R, Ramael S, Bulitta M, van der Hoeven JG (2009) Clinical pharmacology of exogenously administered alkaline phosphatase. Eur J Clin Pharmacol 65:393–402.  https://doi.org/10.1007/s00228-008-0591-6 CrossRefPubMedGoogle Scholar
  125. Pickkers P, Heemskerk S, Schouten J, Laterre PF, Vincent JL, Beishuizen A, Jorens PG, Spapen H, Bulitta M, Peters WHM, van der Hoeven JG (2012) Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial. Crit Care 16:R14.  https://doi.org/10.1186/cc11159 CrossRefPubMedPubMedCentralGoogle Scholar
  126. Pike AF, Kramer NI, Blaauboer BJ, Seinen W, Brands R (2015) An alkaline phosphatase transport mechanism in the pathogenesis of Alzheimer’s disease and neurodegeneration. Chem Biol Interact 226:30–39.  https://doi.org/10.1016/j.cbi.2014.12.006 CrossRefPubMedGoogle Scholar
  127. Pineda S, Bang OY, Saver JL, Starkman S, Yun SW, Liebeskind DS, Kim D, Ali LK, Shah SH, Ovbiagele B (2008) Association of Serum Bilirubin with ischemic stroke outcomes. J Stroke Cerebrovasc Dis 17:147–152.  https://doi.org/10.1016/j.jstrokecerebrovasdis.2008.01.009 CrossRefPubMedPubMedCentralGoogle Scholar
  128. Poelstra K, Bakker WW, Klok PA, Hardonk MJ, Meijer DK (1997a) A physiologic function for alkaline phosphatase: endotoxin detoxification. Lab Investig 76:319–327PubMedGoogle Scholar
  129. Poelstra K, Bakker WW, Klok PA, Hardonk MJ (1997b) Dephosphorylation of endotoxin by alkaline phosphatase in vivo. Am J Pathol 151:1163–1169PubMedPubMedCentralGoogle Scholar
  130. Posen S, Neale FC, Birkett DJ, Brudenell-Woods J (1967) Intestinal alkaline phosphatase in human serum. Am J Clin Pathol 48:81–86.  https://doi.org/10.1093/ajcp/48.1.81 CrossRefPubMedGoogle Scholar
  131. Pratibha S, Praveen-Kumar S, Agadi JB (2014) Increased serum alkaline phosphatase and serum phosphate as predictors of mortality after stroke. J Clin Diagn Res 8:CC01–CC03.  https://doi.org/10.7860/jcdr/2014/8350.4649 CrossRefGoogle Scholar
  132. Razazizan N, Mirmoeini M, Daeichin S, Ghadiri K (2013) Comparison of 25-Hydroxy vitamin D, calcium and alkaline phosphatase levels in epileptic and non-epileptic children. Acta Neurol Taiwanica 22:112–116Google Scholar
  133. Rentea RM, Liedel JL, Welak SR, Cassidy LD, Mayer AN, Pritchard KA Jr, Oldham KT, Gourlay DM (2012) Intestinal alkaline phosphatase administration in newborns is protective of gut barrier function in a neonatal necrotizing enterocolitis rat model. J Pediatr Surg 47:1135–1142.  https://doi.org/10.1016/j.jpedsurg.2012.03.018 CrossRefPubMedGoogle Scholar
  134. Rentea RM, Liedel JL, Fredrich K, Pritchard K Jr, Oldham KT, Simpson PM, Gourlay DM (2013) Enteral intestinal alkaline phosphatase administration in newborns decreases iNOS expression in a neonatal necrotizing enterocolitis rat model. J Pediatr Surg 48:124–128.  https://doi.org/10.1016/j.jpedsurg.2012.10.026 CrossRefPubMedPubMedCentralGoogle Scholar
  135. Report of the Quality Standards Subcommittee of the American Academy of Neurology (1996) Practice advisory: thrombolytic therapy for acute ischemic stroke--summary statement. Neurology 47:835–839.  https://doi.org/10.1212/WNL.47.3.835 CrossRefGoogle Scholar
  136. Robison R (1923) The possible significance of hexosephosphoric esters in ossification. Biochem J 17:286–293CrossRefGoogle Scholar
  137. Rodin A, Duncan A, Quartero HWP et al (1989) Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in Normal pregnancy*. J Clin Endocrinol Metab 68:1123–1127.  https://doi.org/10.1210/jcem-68-6-1123 CrossRefPubMedGoogle Scholar
  138. Romanelli F, Corbo A, Salehi M, Yadav MC, Salman S, Petrosian D, Rashidbaigi OJ, Chait J, Kuruvilla J, Plummer M, Radichev I, Margulies KB, Gerdes AM, Pinkerton AB, Millán JL, Savinov AY, Savinova OV (2017) Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia. PLoS One 12:e0186426.  https://doi.org/10.1371/journal.pone.0186426 CrossRefPubMedPubMedCentralGoogle Scholar
  139. Ryu W-S, Lee S-H, Kim CK, Kim BJ, Yoon BW (2010) Increased serum alkaline phosphatase as a predictor of long-term mortality after stroke. Neurology 75:1995–2002.  https://doi.org/10.1212/WNL.0b013e3181ff966a CrossRefPubMedGoogle Scholar
  140. Ryu W-S, Lee S-H, Kim CK, Kim BJ, Kwon HM, Yoon BW (2014) High serum alkaline phosphatase in relation to cerebral small vessel disease. Atherosclerosis 232:313–318.  https://doi.org/10.1016/j.atherosclerosis.2013.11.047 CrossRefPubMedGoogle Scholar
  141. Sadighi A, Roshan MM, Moradi A, Ostadrahimi A (2008) The effects of zinc supplementation on serum zinc, alkaline phosphatase activity and fracture healing of bones. Saudi Med J 29:1276–1279PubMedGoogle Scholar
  142. Schiff A, Yang J, Winner LH, Schwartz MC (2016) Bone-specific alkaline phosphatase in patients who have undergone the Fontan operation. Pediatr Cardiol 37:1370–1376.  https://doi.org/10.1007/s00246-016-1443-2 CrossRefPubMedGoogle Scholar
  143. Schlaeger R (1975) The mechanism of the increase in the activity of liver alkaline phosphatase in experimental cholestasis: measurement of an increased enzyme concentration by immunochemical titration. Z Klin Chem Klin Biochem 13:277–281PubMedGoogle Scholar
  144. Schmidt-Lucke C, Rössig L, Fichtlscherer S, Vasa M, Britten M, Kämper U, Dimmeler S, Zeiher AM (2005) Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events. Circulation 111:2981–2987.  https://doi.org/10.1161/circulationaha.104.504340 CrossRefPubMedGoogle Scholar
  145. Sebastián-Serrano Á, Engel T, de Diego-García L, Olivos-Oré LA, Arribas-Blázquez M, Martínez-Frailes C, Pérez-Díaz C, Millán JL, Artalejo AR, Miras-Portugal MT, Henshall DC, Díaz-Hernández M (2016) Neurodevelopmental alterations and seizures developed by mouse model of infantile hypophosphatasia are associated with purinergic signalling deregulation. Hum Mol Genet 25:4143–4156.  https://doi.org/10.1093/hmg/ddw248 CrossRefPubMedPubMedCentralGoogle Scholar
  146. Sheen CR, Kuss P, Narisawa S, Yadav MC, Nigro J, Wang W, Chhea TN, Sergienko EA, Kapoor K, Jackson MR, Hoylaerts MF, Pinkerton AB, O'Neill WC, Millán JL (2015) Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification. J Bone Miner Res 30:824–836.  https://doi.org/10.1002/jbmr.2420 CrossRefPubMedPubMedCentralGoogle Scholar
  147. Shimizu N (1950) Histochemical studies on the phosphatase of the nervous system. J Comp Neurol 93:201–217.  https://doi.org/10.1002/cne.900930203 CrossRefPubMedGoogle Scholar
  148. Shimizu Y, Imano H, Ohira T, Kitamura A, Kiyama M, Okada T, Ishikawa Y, Shimamoto T, Yamagishi K, Tanigawa T, Iso H, CIRCS Investigators (2013a) Alkaline phosphatase and risk of stroke among Japanese: the circulatory risk in communities study (CIRCS). J Stroke Cerebrovasc Dis 22:1046–1055.  https://doi.org/10.1016/j.jstrokecerebrovasdis.2012.06.009 CrossRefPubMedGoogle Scholar
  149. Shimizu Y, Nakazato M, Sekita T, Kadota K, Yamasaki H, Takamura N, Aoyagi K, Kusano Y, Maeda T (2013b) Association between alkaline phosphatase and hypertension in a rural Japanese population: the Nagasaki Islands study. J Physiol Anthropol 32:10.  https://doi.org/10.1186/1880-6805-32-10 CrossRefPubMedPubMedCentralGoogle Scholar
  150. Shioi A, Katagi M, Okuno Y, Mori K, Jono S, Koyama H, Nishizawa Y (2002) Induction of bone-type alkaline phosphatase in human vascular smooth muscle cells. Circ Res 91:9–16.  https://doi.org/10.1161/01.res.0000026421.61398.f2 CrossRefPubMedGoogle Scholar
  151. Sigrist MK, McIntyre CW (2008) Vascular calcification is associated with impaired microcirculatory function in chronic haemodialysis patients. Nephron Clin Pract 108:121–126.  https://doi.org/10.1159/000114202 CrossRefGoogle Scholar
  152. Sonderer J, Katan Kahles M (2015) Aetiological blood biomarkers of ischaemic stroke. Swiss Med Wkly 145:w14138.  https://doi.org/10.4414/smw.2015.14138 CrossRefPubMedGoogle Scholar
  153. Su F, Brands R, Wang Z, Verdant C, Bruhn A, Cai Y, Raaben W, Wulferink M, Vincent JL (2006) Beneficial effects of alkaline phosphatase in septic shock. Crit Care Med 34:2182–2187.  https://doi.org/10.1097/01.CCM.0000229887.70579.29 CrossRefPubMedGoogle Scholar
  154. Sukumaran M, Bloom WL (1953) Influence of diet on serum alkaline phosphatase in rats and men. Exp Biol Med 84:631–634.  https://doi.org/10.3181/00379727-84-20735 CrossRefGoogle Scholar
  155. Taal B, Tinteren HV, Zoetmulder F (2001) Adjuvant 5FU plus levamisole in colonic or rectal cancer:improved survival in stage II and III. Br J Cancer 85:1437–1443.  https://doi.org/10.1054/bjoc.2001.2117 CrossRefGoogle Scholar
  156. Taguchi A, Matsuyama T, Moriwaki H, Hayashi T, Hayashida K, Nagatsuka K, Todo K, Mori K, Stern DM, Soma T, Naritomi H (2004) Circulating CD34-positive cells provide an index of cerebrovascular function. Circulation 109:2972–2975.  https://doi.org/10.1161/01.cir.0000133311.25587.de CrossRefPubMedGoogle Scholar
  157. Tan G, Hao Z, Lei C, Chen Y, Yuan R, Xu M, Liu M (2016) Subclinical change of liver function could also provide a clue on prognosis for patients with spontaneous intracerebral hemorrhage. Neurol Sci 37:1693–1700.  https://doi.org/10.1007/s10072-016-2656-0 CrossRefPubMedGoogle Scholar
  158. Tan L-M, Wang L, Chen J-J, Li H, Luo WB (2017) Diagnostic performance of bone metabolic indexes for the detection of stroke. Saudi Med J 37:30–35.  https://doi.org/10.15537/smj.2017.1.15813 CrossRefGoogle Scholar
  159. Tang WK, Liang H, Chu WCW, Mok V, Ungvari GS, Wong KS (2013) Association between high serum total bilirubin and post-stroke depression. Psychiatry Clin Neurosci 67:259–264.  https://doi.org/10.1111/pcn.12051 CrossRefPubMedGoogle Scholar
  160. Teitelbaum JE, Laskowski A, Barrows FP (2011) Benign transient hyperphosphatasemia in infants and children: a prospective cohort. J Pediatr Endocrinol Metab 24:351–353CrossRefGoogle Scholar
  161. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333:1581–1587.  https://doi.org/10.1056/NEJM199512143332401 CrossRefGoogle Scholar
  162. Tonelli M, Curhan G, Pfeffer M, Sacks F, Thadhani R, Melamed ML, Wiebe N, Muntner P (2009) Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality. Circulation 120:1784–1792.  https://doi.org/10.1161/circulationaha.109.851873 CrossRefPubMedGoogle Scholar
  163. Tremlett H, Seemuller S, Zhao Y, Yoshida EM, Oger J, Petkau J (2006) Liver test abnormalities in multiple sclerosis: findings from placebo-treated patients. Neurology 67:1291–1293.  https://doi.org/10.1212/01.wnl.0000238515.27055.62 CrossRefPubMedGoogle Scholar
  164. Tuin A, Poelstra K, de Jager-Krikken A, Bok L, Raaben W, Velders MP, Dijkstra G (2009) Role of alkaline phosphatase in colitis in man and rats. Gut 58:379–387.  https://doi.org/10.1136/gut.2007.128868 CrossRefPubMedGoogle Scholar
  165. Uehara T, Ohara T, Minematsu K, Nagatsuka K, Toyoda K (2018) Predictors of stroke events in patients with transient ischemic attack attributable to intracranial stenotic lesions. Intern Med 57:295–300.  https://doi.org/10.2169/internalmedicine.9447-17 CrossRefPubMedGoogle Scholar
  166. Van Hoof V, De Broe M (1994) Interpretation and clinical significance of alkaline phosphatase isoenzyme patterns. Crit Rev Clin Lab Sci 31:197–293.  https://doi.org/10.3109/10408369409084677 CrossRefPubMedGoogle Scholar
  167. van Veen SQ, van Vliet AK, Wulferink M, Brands R, Boermeester MA, van Gulik TM (2005) Bovine intestinal alkaline phosphatase attenuates the inflammatory response in secondary peritonitis in mice. Infect Immun 73:4309–4314.  https://doi.org/10.1128/IAI.73.7.4309-4314.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  168. Vardy ER, Kellett KA, Cocklin SL, Hooper NM (2012) Alkaline phosphatase is increased in both brain and plasma in Alzheimer’s disease. Neurodegener Dis 9:31–37.  https://doi.org/10.1159/000329722 CrossRefPubMedGoogle Scholar
  169. Vernino S, Brown RD, Sejvar JJ, Sicks JD, Petty GW, O'Fallon WM (2003) Cause-specific mortality after first cerebral infarction: a population-based study. Stroke 34:1828–1832.  https://doi.org/10.1161/01.STR.0000080534.98416.A0 CrossRefPubMedGoogle Scholar
  170. Verweij WR, Bentala H, Huizinga-van der Vlag A et al (2004) Protection against an Escherichia coli-induced sepsis by alkaline phosphatase in mice. Shock 22:174–179CrossRefGoogle Scholar
  171. Wanjian G, Jie H, Liang G, Cheng W, Tian X, Jianjiang S, Chunni Z (2017) Establishment of reference interval for alkaline phosphatase in healthy children of various ethnicities, aged 0-12 years. Lab Med 48:166–171.  https://doi.org/10.1093/labmed/lmx017 CrossRefPubMedGoogle Scholar
  172. Wannamethee SG, Sattar N, Papcosta O, Lennon L, Whincup PH (2013) Alkaline phosphatase, serum phosphate, and incident cardiovascular disease and Total mortality in older men. Arterioscler Thromb Vasc Biol 33:1070–1076.  https://doi.org/10.1161/atvbaha.112.300826 CrossRefPubMedGoogle Scholar
  173. Waymire KG, Mahuren JD, Jaje JM, Guilarte TR, Coburn SP, MacGregor GR (1995) Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6. Nat Genet 11:45–51CrossRefGoogle Scholar
  174. Webber M, Krishnan A, Thomas NG, Cheung BM (2010) Association between serum alkaline phosphatase and C-reactive protein in the United States National Health and nutrition examination survey 2005-2006. Clin Chem Lab Med 48:167–173.  https://doi.org/10.1515/cclm.2010.052 CrossRefPubMedGoogle Scholar
  175. Weiss MJ, Henthorn PS, Lafferty MA, Slaughter C, Raducha M, Harris H (1986) Isolation and characterization of a cDNA encoding a human liver/bone/kidney-type alkaline phosphatase. Proc Natl Acad Sci 83:7182–7186.  https://doi.org/10.1073/pnas.83.19.7182 CrossRefPubMedGoogle Scholar
  176. Whitehouse JS, Riggle KM, Purpi DP, Mayer AN, Pritchard KA Jr, Oldham KT, Gourlay DM (2010) The protective role of intestinal alkaline phosphatase in necrotizing enterocolitis. J Surg Res 163:79–85.  https://doi.org/10.1016/j.jss.2010.04.048 CrossRefPubMedGoogle Scholar
  177. Whyte MP, Landt IM, Ryan LM et al (1995) Alkaline phosphatase: placental and tissue-nonspecific lsoenzymes hydrolyze Phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5’-phosphate. J Clin Invest 95:1440–1445CrossRefGoogle Scholar
  178. Whyte MP, Wenkert D, McAlister WH et al (2009) Chronic recurrent multifocal osteomyelitis mimicked in childhood Hypophosphatasia. J Bone Miner Res 24:1493–1505.  https://doi.org/10.1359/jbmr.090308 CrossRefPubMedGoogle Scholar
  179. Wolf P (1978) Clinical significance of an increased or decreased serum alkaline phosphatase level. Arch Pathol Lab Med 102:497–501PubMedGoogle Scholar
  180. Yamashita M, Sasaki M, Mii K et al (1989) Measurement of serum alkaline phosphatase isozyme I in brain-damaged patients. Neurol Med Chir (Tokyo) 29:995–998CrossRefGoogle Scholar
  181. Yang Y, Rosenberg GA (2011) Blood–brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke 42:3323–3328.  https://doi.org/10.1161/strokeaha.110.608257 CrossRefPubMedPubMedCentralGoogle Scholar
  182. Yoneda M, Takatsuki K, Yamauchi K et al (1988) Effect of parathyroid function on serum bone Gla protein. Endocrinol Jpn 35:39–45.  https://doi.org/10.1507/endocrj1954.35.39 CrossRefPubMedGoogle Scholar
  183. Zhong C, You S, Chen J et al (2018) Serum alkaline phosphatase, phosphate, and in-hospital mortality in acute ischemic stroke patients. J Stroke Cerebrovasc Dis 27:257–266.  https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.08.041 CrossRefPubMedGoogle Scholar
  184. Zhu XY, Gu XJ, Chang JB, Zhang Y, Feng YH, Yin GQ (2004) Changes of blood-cerebrospinal fluid barrier in rabbits with diabetic ketoacidosis. Chinese Critical Care Medicine 16:175–178PubMedGoogle Scholar
  185. Ziegler SG, Ferreira CR, MacFarlane EG et al (2017) Ectopic calcification in pseudoxanthoma elasticum responds to inhibition of tissue-nonspecific alkaline phosphatase. Sci Transl Med 9:eaal1669.  https://doi.org/10.1126/scitranslmed.aal1669 CrossRefPubMedPubMedCentralGoogle Scholar
  186. Zierk J, Arzideh F, Haeckel R, Cario H, Frühwald MC, Groß HJ, Gscheidmeier T, Hoffmann R, Krebs A, Lichtinghagen R, Neumann M, Ruf HG, Steigerwald U, Streichert T, Rascher W, Metzler M, Rauh M (2017) Pediatric reference intervals for alkaline phosphatase. Clin Chem Lab Med 55:102–110.  https://doi.org/10.1515/cclm-2016-0318 CrossRefGoogle Scholar
  187. Zong L, Wang X, Li Z, Zhao X, Liu L, Li H, Meng X, Wang Y, Wang Y (2018) Alkaline phosphatase and outcomes in patients with preserved renal function: results from China National Stroke Registry. Stroke 49:1176–1182.  https://doi.org/10.1161/STROKEAHA.118.020237 CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Microbiology, Immunology, and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience InstituteWest Virginia University School of MedicineMorgantownUSA
  2. 2.Department of Neuroscience, Emergency Medicine, and Microbiology, Immunology and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience InstituteWest Virginia University School of MedicineMorgantownUSA

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