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Review

Progress Towards a Consensus on Biomarkers for Alzheimer‘S Disease: A Review of Peripheral Analytes

, , , , , , & show all
Pages 641-662 | Published online: 02 Aug 2013

References

  • Barnes DE , YaffeK. The projected effect of risk factor reduction on Alzheimer‘s disease prevalence. Lancet Neurol.10(9), 819–828 (2011).
  • Alzheimer‘s Association. 2012 Alzheimer‘s disease facts and figures. Alzheimers Dement.8(2), 131–168 (2012).
  • Dubois B , FeldmanHH, JacovaCet al. Research criteria for the diagnosis of Alzheimer‘s disease: revising the NINCDS–ADRDA criteria. Lancet Neurol. 6(8), 734–746 (2007).
  • Haass C , SelkoeDJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer‘s amyloid beta-peptide. Nat. Rev. Mol. Cell Biol.8(2), 101–112 (2007).
  • Dinamarca MC , RiosJA, InestrosaNC. Postsynaptic receptors for amyloid-beta oligomers as mediators of neuronal damage in Alzheimer‘s disease. Front. Physiol.3, 464 (2012).
  • Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther.69(3), 89–95 (2001).
  • Klunk WE . Biological markers of Alzheimer‘s disease. Neurobiol. Aging19(2), 145–147 (1998).
  • Humpel C . Identifying and validating biomarkers for Alzheimer‘s disease. Trends Biotechnol.29(1), 26–32 (2011).
  • Blennow K , HampelH, WeinerM, ZetterbergH. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat. Rev. Neurol.6(3), 131–144 (2010).
  • Marksteiner J , HinterhuberH, HumpelC. Cerebrospinal fluid biomarkers for diagnosis of Alzheimer‘s disease: beta-amyloid(1–42), tau, phospho-tau-181 and total protein. Drugs Today43(6), 423–431 (2007).
  • Peskind ER , RiekseR, QuinnJFet al. Safety and acceptability of the research lumbar puncture. Alzheimer Dis. Assoc. Disord. 19(4), 220–225 (2005).
  • Thambisetty M , LovestoneS. Blood-based biomarkers of Alzheimer‘s disease: challenging but feasible. Biomarkers Med.4(1), 65–79 (2010).
  • Jelic V , HagmanG, YamamotoNGet al. Abnormal platelet amyloid-beta protein precursor (AbetaPP) metabolism in Alzheimer‘s disease: identification and characterization of a new AbetaPP isoform as potential biomarker. J. Alzheimers Dis. 35(2), 285–295 (2013).
  • Casoli T , BaliettiM, GiorgettiB, SolazziM, ScarpinoO, FattorettiP. Platelets in Alzheimer‘s disease-associated cellular senescence and inflammation. Curr. Pharm. Des.19(9), 1727–1738 (2013).
  • Catricala S , TortiM, RicevutiG. Alzheimer disease and platelets: how‘s that relevant. Immun. Ageing9(1), 20 (2012).
  • Hye A , LynhamS, ThambisettyMet al. Proteome-based plasma biomarkers for Alzheimer‘s disease. Brain 129(11), 3042–3050 (2006).
  • Tammen H , SchulteI, HessRet al. Peptidomic analysis of human blood specimens: comparison between plasma specimens and serum by differential peptide display. Proteomics 5(13), 3414–3422 (2005).
  • Patel S , ShahRJ, ColemanP, SabbaghM. Potential peripheral biomarkers for the diagnosis of Alzheimer‘s disease. Int. J. Alzheimers Dis.2011, 572495 (2011).
  • Zipser BD , JohansonCE, GonzalezLet al. Microvascular injury and blood–brain barrier leakage in Alzheimer‘s disease. Neurobiol. Aging 28(7), 977–986 (2007).
  • Hye A , LynhamS, ThambisettyMet al. Proteome-based plasma biomarkers for Alzheimer‘s disease. Brain 129(Pt 11), 3042–3050 (2006).
  • Aluise CD , SowellRA, ButterfieldDA. Peptides and proteins in plasma and cerebrospinal fluid as biomarkers for the prediction, diagnosis, and monitoring of therapeutic efficacy of Alzheimer‘s disease. Biochim. Biophys. Acta1782(10), 549–558 (2008).
  • Millioni R , TolinS, PuricelliLet al. High abundance proteins depletion vs low abundance proteins enrichment: comparison of methods to reduce the plasma proteome complexity. PLoS ONE 6(5), e19603 (2011).
  • Liumbruno G , D‘AlessandroA, GrazziniG, ZollaL. Blood-related proteomics. J. Proteomics73(3), 483–507 (2010).
  • Rogers JT , BushAI, ChoHHet al. Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: riboregulation against neural oxidative damage in Alzheimer‘s disease. Biochem. Soc. Trans. 36(Pt 6), 1282–1287 (2008).
  • Masters CL , CappaiR, BarnhamKJ, VillemagneVL. Molecular mechanisms for Alzheimer‘s disease: implications for neuroimaging and therapeutics. J. Neurochem.97(6), 1700–1725 (2006).
  • Tanzi RE , BertramL. Twenty years of the Alzheimer‘s disease amyloid hypothesis: a genetic perspective. Cell120(4), 545–555 (2005).
  • Selkoe DJ . Alzheimer‘s disease: a central role for amyloid. J. Neuropathol. Exp. Neurol.53(5), 438–447 (1994).
  • Chen M , InestrosaNC, RossGS, FernandezHL. Platelets are the primary source of amyloid beta-peptide in human blood. Biochem. Biophys. Res. Commun.213(1), 96–103 (1995).
  • Haass C , SchlossmacherMG, HungAYet al. Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 359(6393), 322–325 (1992).
  • Mehta PD , PirttilaT, PatrickBA, BarshatzkyM, MehtaSP. Amyloid beta protein 1–40 and 1–42 levels in matched cerebrospinal fluid and plasma from patients with Alzheimer disease. Neurosci. Lett.304(1–2), 102–106 (2001).
  • Ghersi-Egea JF , GorevicPD, GhisoJ, FrangioneB, PatlakCS, FenstermacherJD. Fate of cerebrospinal fluid-borne amyloid beta-peptide: rapid clearance into blood and appreciable accumulation by cerebral arteries. J. Neurochem.67(2), 880–883 (1996).
  • Shibata M , YamadaS, KumarSRet al. Clearance of Alzheimer‘s amyloid-ss(1–40) peptide from brain by LDL receptor-related protein-1 at the blood–brain barrier. J. Clin. Invest. 106(12), 1489–1499 (2000).
  • Mayeux R , HonigLS, TangMXet al. Plasma A[beta]40 and A[beta]42 and Alzheimer‘s disease: relation to age, mortality, and risk. Neurology 61(9), 1185–1190 (2003).
  • Giedraitis V , SundelofJ, IrizarryMCet al. The normal equilibrium between CSF and plasma amyloid beta levels is disrupted in Alzheimer‘s disease. Neurosci. Lett. 427(3), 127–131 (2007).
  • Fagan AM , MintunMA, ShahARet al. Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer‘s disease. EMBO Mol. Med. 1(8–9), 371–380 (2009).
  • Wilson MR , YerburyJJ, PoonS. Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity. Mol. Biosyst.4(1), 42–52 (2008).
  • Song F , PoljakA, ValenzuelaM, MayeuxR, SmytheGA, SachdevPS. Meta-analysis of plasma amyloid-beta levels in Alzheimer‘s disease. J. Alzheimers Dis.26(2), 365–375 (2011).
  • Fukumoto H , TennisM, LocascioJJ, HymanBT, GrowdonJH, IrizarryMC. Age but not diagnosis is the main predictor of plasma amyloid beta-protein levels. Arch. Neurol.60(7), 958–964 (2003).
  • Kosaka T , ImagawaM, SekiKet al. The beta APP717 Alzheimer mutation increases the percentage of plasma amyloid-beta protein ending at A beta42(43). Neurology 48(3), 741–745 (1997).
  • Scheuner D , EckmanC, JensenMet al. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer‘s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer‘s disease. Nat. Med. 2(8), 864–870 (1996).
  • Sobow T , FlirskiM, KloszewskaI, LiberskiPP. Plasma levels of alpha beta peptides are altered in amnestic mild cognitive impairment but not in sporadic Alzheimer‘s disease. Acta Neurobiol. Exp. (Wars.)65(2), 117–124 (2005).
  • Tamaoka A , FukushimaT, SawamuraNet al. Amyloid beta protein in plasma from patients with sporadic Alzheimer‘s disease. J. Neurol. Sci. 141(1–2), 65–68 (1996).
  • Vanderstichele H , Van KerschaverE, HesseCet al. Standardization of measurement of beta-amyloid(1–42) in cerebrospinal fluid and plasma. Amyloid 7(4), 245–258 (2000).
  • Ertekin-Taner N , YounkinLH, YagerDMet al. Plasma amyloid beta protein is elevated in late-onset Alzheimer disease families. Neurology 70(8), 596–606 (2008).
  • Cosentino SA , SternY, SokolovEet al. Plasma ss-amyloid and cognitive decline. Arch. Neurol. 67(12), 1485–1490 (2010).
  • Sundelof J , GiedraitisV, IrizarryMCet al. Plasma beta amyloid and the risk of Alzheimer disease and dementia in elderly men: a prospective, population-based cohort study. Arch. Neurol. 65(2), 256–263 (2008).
  • van Oijen M , HofmanA, SoaresHD, KoudstaalPJ, BretelerMM. Plasma Abeta(1–40) and Abeta(1–42) and the risk of dementia: a prospective case-cohort study. Lancet Neurol.5(8), 655–660 (2006).
  • Laske C , SopovaK, GkotsisCet al. Amyloid-β peptides in plasma and cognitive decline after 1 year follow-up in Alzheimer‘s disease patients. J. Alzheimers Dis. 21(4), 1263–1269 (2010).
  • Mayeux R , TangMX, JacobsDMet al. Plasma amyloid beta-peptide 1–42 and incipient Alzheimer‘s disease. Ann. Neurol. 46(3), 412–416 (1999).
  • Schupf N , TangMX, FukuyamaHet al. Peripheral Abeta subspecies as risk biomarkers of Alzheimer‘s disease. Proc. Natl Acad. Sci. USA 105(37), 14052–14057 (2008).
  • Lewczuk P , KornhuberJ, VanmechelenEet al. Amyloid beta peptides in plasma in early diagnosis of Alzheimer‘s disease: a multicenter study with multiplexing. Exp. Neurol. 223(2), 366–370 (2010).
  • Pesaresi M , LovatiC, BertoraPet al. Plasma levels of beta-amyloid (1–42) in Alzheimer‘s disease and mild cognitive impairment. Neurobiol. Aging 27(6), 904–905 (2006).
  • Schupf N , ZigmanWB, TangMXet al. Change in plasma Ass peptides and onset of dementia in adults with Down syndrome. Neurology 75(18), 1639–1644 (2010).
  • Seppala TT , HerukkaSK, HanninenTet al. Plasma Abeta42 and Abeta40 as markers of cognitive change in follow-up: a prospective, longitudinal, population-based cohort study. J. Neurol. Neurosurg. Psychiatry 81(10), 1123–1127 (2010).
  • Lui JK , LawsSM, LiQXet al. Plasma amyloid-beta as a biomarker in Alzheimer‘s disease: the AIBL study of aging. J. Alzheimers Dis. 20(4), 1233–1242 (2010).
  • Blennow K , De MeyerG, HanssonOet al. Evolution of Abeta42 and Abeta40 levels and Abeta42/Abeta40 ratio in plasma during progression of Alzheimer‘s disease: a multicenter assessment. J. Nutr. Health Aging 13(3), 205–208 (2009).
  • Graff-Radford NR , CrookJE, LucasJet al. Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch. Neurol. 64(3), 354–362 (2007).
  • Lambert JC , Schraen-MaschkeS, RichardFet al. Association of plasma amyloid beta with risk of dementia: the prospective Three-City Study. Neurology 73(11), 847–853 (2009).
  • Yaffe K , WestonA, Graff-RadfordNRet al. Association of plasma beta-amyloid level and cognitive reserve with subsequent cognitive decline. JAMA 305(3), 261–266 (2011).
  • Watt AD , PerezKA, RembachAR, MastersCL, VillemagneVL, BarnhamKJ. Variability in blood-based amyloid-beta assays: the need for consensus on pre-analytical processing. J. Alzheimers Dis.30(2), 323–336 (2012).
  • Fukumoto E , SakaiH, FukumotoS, YagiT, TakagiO, KatoY. Cadherin-related neuronal receptors in incisor development. J. Dent. Res.82(1), 17–22 (2003).
  • Arvanitakis Z , LucasJA, YounkinLH, YounkinSG, Graff-RadfordNR. Serum creatinine levels correlate with plasma amyloid beta protein. Alzheimer Dis. Assoc. Disord.16(3), 187–190 (2002).
  • Kuller LH , LongstrethWTJr, ArnoldAM, BernickC, BryanRN, BeauchampNJ Jr. White matter hyperintensity on cranial magnetic resonance imaging: a predictor of stroke. Stroke 35(8), 1821–1825 (2004).
  • Lopez OL , KullerLH, MehtaPDet al. Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study. Neurology 70(19), 1664–1671 (2008).
  • Blasko I , KemmlerG, KramplaWet al. Plasma amyloid beta protein 42 in non-demented persons aged 75 years: effects of concomitant medication and medial temporal lobe atrophy. Neurobiol. Aging 26(8), 1135–1143 (2005).
  • Toledo JB , VandersticheleH, FigurskiMet al. Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI. Acta Neuropathologica 122(4), 401–413 (2011).
  • Rembach A , FauxNG, WattADet al. Changes in plasma amyloid beta in a longitudinal study of aging and Alzheimer‘s disease. Alzheimers Dement. doi:10.1016/j.jalz.2012.12.006 (2013) (Epub ahead of print).
  • Villemagne VL , PerezKA, PikeKEet al. Blood borne Amyloid-beta dimer correlates with clinical markers of Alzheimer‘s disease. J. Neurosci. 30(18), 6315–6322 (2010).
  • Watt AD , PerezKA, FauxNGet al. Increasing the predictive accuracy of amyloid-β blood-borne biomarkers in Alzheimer‘s disease. J. Alzheimers Dis. 24(1), 47–59 (2010).
  • Pesini P , Perez-GrijalbaV, MonleonIet al. Reliable measurements of the β-amyloid pool in blood could help in the early diagnosis of AD. Int. J. Alzheimers Dis. 604141 (2012).
  • Kiko T , NakagawaK, SatohAet al. Amyloid beta levels in human red blood cells. PLoS ONE 7(11), e49620 (2012).
  • Mattson MP , BegleyJG, MarkRJ, FurukawaK. Abeta25–35 induces rapid lysis of red blood cells: contrast with Abeta1–42 and examination of underlying mechanisms. Brain Res.771(1), 147–153 (1997).
  • Mohanty JG , EckleyDM, WilliamsonJD, LaunerLJ, RifkindJM. Do red blood cell-beta-amyloid interactions alter oxygen delivery in Alzheimer‘s disease?Adv. Exp. Med. Biol.614, 29–35 (2008).
  • Nakagawa K , KikoT, KuriwadaS, MiyazawaT, KimuraF. Amyloid β induces adhesion of erythrocytes to endothelial cells and affects endothelial viability and functionality. Biosci. Biotechnol. Biochem.75(10), 2030–2033 (2011).
  • Kosicek M , HecimovicS. Phospholipids and Alzheimer‘s disease: alterations, mechanisms and potential biomarkers. Int. J. Mol. Sci.14(1), 1310–1322 (2013).
  • Svennerholm L , BostromK, HelanderCG, JungbjerB. Membrane lipids in the aging human brain. J. Neurochem.56(6), 2051–2059 (1991).
  • Bjorkhem I . Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J. Intern. Med.260(6), 493–508 (2006).
  • Pike LJ . The challenge of lipid rafts. J. Lipid Res.50(Suppl.), S323–S328 (2009).
  • Hicks DA , NalivaevaNN, TurnerAJ. Lipid rafts and Alzheimer‘s disease: protein–lipid interactions and perturbation of signaling. Front. Physiol.3, 189 (2012).
  • Pernber Z , BlennowK, BogdanovicN, ManssonJE, BlomqvistM. Altered distribution of the gangliosides GM1 and GM2 in Alzheimer‘s disease. Dement. Geriat. Cogn. Disord.33(2–3), 174–188 (2012).
  • Mahley RW . Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science240(4852), 622–630 (1988).
  • Hoe HS , RebeckGW. Regulated proteolysis of APP and ApoE receptors. Mol. Neurobiol.37(1), 64–72 (2008).
  • Elliott DA , TsoiK, HolinkovaSet al. Isoform-specific proteolysis of apolipoprotein-E in the brain. Neurobiol. Aging 32(2), 257–271 (2011).
  • Zhou W , ScottSA, SheltonSB, CrutcherKA. Cathepsin D-mediated proteolysis of apolipoprotein E: possible role in Alzheimer‘s disease. Neuroscience143(3), 689–701 (2006).
  • Castano EM , PrelliF, PrasM, FrangioneB. Apolipoprotein E carboxyl-terminal fragments are complexed to amyloids A and L. Implications for amyloidogenesis and Alzheimer‘s disease. J. Biol. Chem.270(29), 17610–17615 (1995).
  • Tolar M , MarquesMA, HarmonyJA, CrutcherKA. Neurotoxicity of the 22 kDa thrombin-cleavage fragment of apolipoprotein E and related synthetic peptides is receptor-mediated. J. Neurosci.17(15), 5678–5686 (1997).
  • Panegyres PK , GoldblattJ, WalpoleI, ConnorC, LiebeckT, HarropK. Genetic testing for Alzheimer‘s disease. Med. J. Aust.172(7), 339–343 (2000).
  • Akuffo EL , DavisJB, FoxSMet al. The discovery and early validation of novel plasma biomarkers in mild-to-moderate Alzheimer‘s disease patients responding to treatment with rosiglitazone. Biomarkers 13(6), 618–636 (2008).
  • Taddei K , ClarnetteR, GandySE, MartinsRN. Increased plasma apolipoprotein E (apoE) levels in Alzheimer‘s disease. Neurosci. Lett.223(1), 29–32 (1997).
  • Lehtimaki T , PirttilaT, MehtaPD, WisniewskiHM, FreyH, NikkariT. Apolipoprotein E (ApoE) polymorphism and its influence on ApoE concentrations in the cerebrospinal fluid in Finnish patients with Alzheimer‘s disease. Hum. Genet.95(1), 39–42 (1995).
  • Gupta VB , LawsSM, VillemagneVLet al. Plasma apolipoprotein E and Alzheimer disease risk: the AIBL study of aging. Neurology 76(12), 1091–1098 (2011).
  • Siest G , BertrandP, HerbethBet al. Apolipoprotein E polymorphisms and concentration in chronic diseases and drug responses. Clin. Chem. Lab. Med. 38(9), 841–852 (2000).
  • Fukumoto H , IngelssonM, GarevikNet al. APOE epsilon 3/epsilon 4 heterozygotes have an elevated proportion of apolipoprotein E4 in cerebrospinal fluid relative to plasma, independent of Alzheimer‘s disease diagnosis. Exp. Neurol.183(1), 249–253 (2003).
  • Pfrieger FW . Cholesterol homeostasis and function in neurons of the central nervous system. Cell. Mol. Life Sci.60(6), 1158–1171 (2003).
  • Pitas RE , BoylesJK, LeeSH, HuiD, WeisgraberKH. Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. J. Biol. Chem.262(29), 14352–14360 (1987).
  • Kivipelto M , NganduT, FratiglioniLet al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch. Neurol. 62(10), 1556–1560 (2005).
  • Notkola IL , SulkavaR, PekkanenJet al. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer‘s disease. Neuroepidemiology 17(1), 14–20 (1998).
  • Whitmer RA , SidneyS, SelbyJ, JohnstonSC, YaffeK. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology64(2), 277–281 (2005).
  • Stewart R , WhiteLR, XueQL, LaunerLJ. Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu–Asia Aging Study. Arch. Neurol.64(1), 103–107 (2007).
  • Beydoun MA , Beason-HeldLL, Kitner-TrioloMHet al. Statins and serum cholesterol‘s associations with incident dementia and mild cognitive impairment. J. Epidemiol. Community Health 65(11), 949–957 (2011).
  • Li G , ShoferJB, KukullWAet al. Serum cholesterol and risk of Alzheimer disease: a community-based cohort study. Neurology 65(7), 1045–1050 (2005).
  • Mainous AG 3rd, EschenbachSL, WellsBJ, EverettCJ, GillJM. Cholesterol, transferrin saturation, and the development of dementia and Alzheimer‘s disease: results from an 18-year population-based cohort. Fam. Med. 37(1), 36–42 (2005).
  • Romas SN , TangMX, BerglundL, MayeuxR. APOE genotype, plasma lipids, lipoproteins, and AD in community elderly. Neurology53(3), 517–521 (1999).
  • Tan ZS , SeshadriS, BeiserAet al. Plasma total cholesterol level as a risk factor for Alzheimer disease: the Framingham Study. Arch. Intern. Med. 163(9), 1053–1057 (2003).
  • Sato Y , SuzukiI, NakamuraT, BernierF, AoshimaK, OdaY. Identification of a new plasma biomarker of Alzheimer‘s disease using metabolomics technology. J. Lipid Res.53(3), 567–576 (2012).
  • Wong WB , LinVW, BoudreauD, DevineEB. Statins in the prevention of dementia and Alzheimer‘s disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiol. Drug Saf.22(4), 345–358 (2013).
  • Leoni V . Oxysterols as markers of neurological disease – a review. Scand. J. Clin. Lab. Invest.69(1), 22–25 (2009).
  • Hughes TM , RosanoC, EvansRW, KullerLH. Brain cholesterol metabolism, oxysterols, and dementia. J. Alzheimers Dis.33(4), 891–911 (2013).
  • Han X , M HoltzmanD, McKeelDW Jr, KelleyJ, MorrisJC. Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer‘s disease: potential role in disease pathogenesis. J. Neurochem. 82(4), 809–818 (2002).
  • Cutler RG , KellyJ, StorieKet al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer‘s disease. Proc. Natl Acad. Sci. USA 101(7), 2070–2075 (2004).
  • He X , HuangY, LiB, GongCX, SchuchmanEH. Deregulation of sphingolipid metabolism in Alzheimer‘s disease. Neurobiol. Aging31(3), 398–408 (2010).
  • Han X , RozenS, BoyleSHet al. Metabolomics in early Alzheimer‘s disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS ONE 6(7), e21643 (2011).
  • Mielke MM , HaugheyNJ, Ratnam BandaruVVet al. Plasma ceramides are altered in mild cognitive impairment and predict cognitive decline and hippocampal volume loss. Alzheimers Dement. 6(5), 378–385 (2010).
  • Mielke MM , BandaruVV, HaugheyNJet al. Serum ceramides increase the risk of Alzheimer disease: the Women‘s Health and Aging Study II. Neurology 79(7), 633–641 (2012).
  • Li NJ , LiuWT, LiWet al. Plasma metabolic profiling of Alzheimer‘s disease by liquid chromatography/mass spectrometry. Clin. Biochem. 43(12), 992–997 (2010).
  • Wallin A , GottfriesCG, KarlssonI, SvennerholmL. Decreased myelin lipids in Alzheimer‘s disease and vascular dementia. Acta Neurol. Scand.80(4), 319–323 (1989).
  • Dross K , KewitzH. Concentration and origin of choline in the rat brain. Naunyn Schmiedebergs Arch. Pharmacol.274(1), 91–106 (1972).
  • Igarashi M , MaK, GaoF, KimHW, RapoportSI, RaoJS. Disturbed choline plasmalogen and phospholipid fatty acid concentrations in Alzheimer‘s disease prefrontal cortex. J. Alzheimers Dis.24(3), 507–517 (2011).
  • Walter A , KorthU, HilgertMet al. Glycerophosphocholine is elevated in cerebrospinal fluid of Alzheimer patients. Neurobiol. Aging 25(10), 1299–1303 (2004).
  • Nitsch RM , BlusztajnJK, PittasAG, SlackBE, GrowdonJH, WurtmanRJ. Evidence for a membrane defect in Alzheimer disease brain. Proc. Natl Acad. Sci. USA89(5), 1671–1675 (1992).
  • Ellison DW , BealMF, MartinJB. Phosphoethanolamine and ethanolamine are decreased in Alzheimer‘s disease and Huntington‘s disease. Brain Res.417(2), 389–392 (1987).
  • Molina JA , Jimenez-JimenezFJ, VargasCet al. Cerebrospinal fluid levels of non-neurotransmitter amino acids in patients with Alzheimer‘s disease. J. Neural Transm. 105(2–3), 279–286 (1998).
  • Ginsberg L , RafiqueS, XuerebJH, RapoportSI, GershfeldNL. Disease and anatomic specificity of ethanolamine plasmalogen deficiency in Alzheimer‘s disease brain. Brain Res.698(1–2), 223–226 (1995).
  • Han X , HoltzmanDM, McKeelDWJr. Plasmalogen deficiency in early Alzheimer‘s disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry. J. Neurochem. 77(4), 1168–1180 (2001).
  • Han X . Lipid alterations in the earliest clinically recognizable stage of Alzheimer‘s disease: implication of the role of lipids in the pathogenesis of Alzheimer‘s disease. Curr. Alzheimer Res.2(1), 65–77 (2005).
  • Goodenowe DB , CookLL, LiuJet al. Peripheral ethanolamine plasmalogen deficiency: a logical causative factor in Alzheimer‘s disease and dementia. J. Lipid Res. 48(11), 2485–2498 (2007).
  • Wood PL , MankidyR, RitchieSet al. Circulating plasmalogen levels and Alzheimer Disease Assessment Scale–Cognitive scores in Alzheimer patients. J. Phychiatry Neurosci. 35(1), 59–62 (2010).
  • Pratico D . The neurobiology of isoprostanes and Alzheimer‘s disease. Biochim. Biophys. Acta1801(8), 930–933 (2010).
  • Lovell MA , MarkesberyWR. Oxidative damage in mild cognitive impairment and early Alzheimer‘s disease. J. Neurosci. Res.85(14), 3036–3040 (2007).
  • Montine TJ , QuinnJ, KayeJ, MorrowJD. F(2)-isoprostanes as biomarkers of late-onset Alzheimer‘s disease. J. Mol. Neurosci.33(1), 114–119 (2007).
  • Pratico D , ClarkCM, LeeVM, TrojanowskiJQ, RokachJ, FitzgeraldGA. Increased 8,12-iso-iPF2alpha-VI in Alzheimer‘s disease: correlation of a noninvasive index of lipid peroxidation with disease severity. Ann. Neurol.48(5), 809–812 (2000).
  • Pratico D , ClarkCM, LiunF, RokachJ, LeeVY, TrojanowskiJQ. Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch. Neurol.59(6), 972–976 (2002).
  • Irizarry MC , YaoY, HymanBT, GrowdonJH, PraticoD. Plasma F2A isoprostane levels in Alzheimer‘s and Parkinson‘s disease. Neurodegene. Dis.4(6), 403–405 (2007).
  • Cooper-Knock J , KirbyJ, FerraiuoloL, HeathPR, RattrayM, ShawPJ. Gene expression profiling in human neurodegenerative disease. Nat. Rev. Neurol.8(9), 518–530 (2012).
  • Booij BB , LindahlT, WetterbergPet al. A gene expression pattern in blood for the early detection of Alzheimer‘s disease. J. Alzheimers Dis. 23(1), 109–119 (2011).
  • Rye PD , BooijBB, GraveGet al. A novel blood test for the early detection of Alzheimer‘s disease. J. Alzheimers Dis. 23(1), 121–129 (2011).
  • Fehlbaum-Beurdeley P , Jarrige-Le PradoAC, PallaresDet al. Toward an Alzheimer‘s disease diagnosis via high-resolution blood gene expression. Alzheimers Dement. 6(1), 25–38 (2010).
  • Lunnon K , SattleckerM, FurneySJet al. A blood gene expression marker of early Alzheimer‘s disease. J. Alzheimers Dis. 33(3), 737–753 (2013).
  • Bellingham SA , GuoBB, ColemanBM, HillAF. Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases?Front. Physiol.3, 124 (2012).
  • Sharples RA , VellaLJ, NisbetRMet al. Inhibition of gamma-secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes. FASEB J. 22(5), 1469–1478 (2008).
  • Geekiyanage H , JichaGA, NelsonPT, ChanC. Blood serum miRNA: non-invasive biomarkers for Alzheimer‘s disease. Exp. Neurol.235(2), 491–496 (2012).
  • Sheinerman KS , TsivinskyVG, CrawfordF, MullanMJ, AbdullahL, UmanskySR. Plasma microRNA biomarkers for detection of mild cognitive impairment. Aging4(9), 590–605 (2012).
  • Adlard PA , BushAI. Metals and Alzheimer‘s disease. J. Alzheimers Dis.10(2–3), 145–163 (2006).
  • Collingwood JF , MikhaylovaA, DavidsonMet al. In situ characterization and mapping of iron compounds in Alzheimer‘s disease tissue. J. Alzheimers Dis.7(4), 267–272 (2005).
  • Deibel MA , EhmannWD, MarkesberyWR. Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer‘s disease: possible relation to oxidative stress. J. Neurol. Sci.143(1–2), 137–142 (1996).
  • Lovell MA , RobertsonJD, TeesdaleWJ, CampbellJL, MarkesberyWR. Copper, iron and zinc in Alzheimer‘s disease senile plaques. J. Neurol. Sci.158(1), 47–52 (1998).
  • Miller LM , WangQ, TelivalaTP, SmithRJ, LanzirottiA, MiklossyJ. Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with beta-amyloid deposits in Alzheimer‘s disease. J. Struct. Biol.155(1), 30–37 (2006).
  • Bush AI , TanziRE. Therapeutics for Alzheimer‘s disease based on the metal hypothesis. Neurotherapeutics5(3), 421–432 (2008).
  • Altamura S , MuckenthalerMU. Iron toxicity in diseases of aging: Alzheimer‘s disease, Parkinson‘s disease and atherosclerosis. J. Alzheimers Dis.16(4), 879–895 (2009).
  • Maynard CJ , CappaiR, VolitakisIet al. Overexpression of Alzheimer‘s disease amyloid-beta opposes the age-dependent elevations of brain copper and iron. J. Biol. Chem. 277(47), 44670–44676 (2002).
  • Bellingham SA , CiccotostoGD, NeedhamBEet al. Gene knockout of amyloid precursor protein and amyloid precursor-like protein-2 increases cellular copper levels in primary mouse cortical neurons and embryonic fibroblasts. J. Neurochem. 91(2), 423–428 (2004).
  • White AR , ReyesR, MercerJFet al. Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Res. 842(2), 439–444 (1999).
  • Bressler JP , OliviL, CheongJH, KimY, MaertenA, BannonD. Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities. Hum. Exp. Toxicol.26(3), 221–229 (2007).
  • Gerhardsson L , LundhT, MinthonL, LondosE. Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer‘s disease. Dement. Geriat. Cogn. Disord.25(6), 508–515 (2008).
  • Gonzalez C , MartinT, CachoJet al. Serum zinc, copper, insulin and lipids in Alzheimer‘s disease epsilon 4 apolipoprotein E allele carriers. Eur. J. Clin. Invest. 29(7), 637–642 (1999).
  • Roberts NB , CloughA, BelliaJP, KimJY. Increased absorption of aluminium from a normal dietary intake in dementia. J. Inorg. Biochem.69(3), 171–176 (1998).
  • Smorgon C , MariE, AttiARet al. Trace elements and cognitive impairment: an elderly cohort study. Arch. Gerontol. Geriatr. Suppl. (9), 393–402 (2004).
  • Squitti R , BarbatiG, RossiLet al. Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF [beta]-amyloid, and h-tau. Neurology 67(1), 76–82 (2006).
  • Squitti R , BressiF, PasqualettiPet al. Longitudinal prognostic value of serum ‘free‘ copper in patients with Alzheimer disease. Neurology 72(1), 50–55 (2009).
  • Taylor GA , FerrierIN, McLoughlinIJet al. Gastrointestinal absorption of aluminium in Alzheimer‘s disease: response to aluminium citrate. Age Ageing 21(2), 81–90 (1992).
  • Vural H , DemirinH, KaraY, ErenI, DelibasN. Alterations of plasma magnesium, copper, zinc, iron and selenium concentrations and some related erythrocyte antioxidant enzyme activities in patients with Alzheimer‘s disease. J. Trace Elem. Med. Biol.24(3), 169–173 (2010).
  • Zapatero MD , Garcia de JalonA, PascualF, CalvoML, EscaneroJ, MarroA. Serum aluminum levels in Alzheimer‘s disease and other senile dementias.Biol. Trace Elem. Res.47(1–3), 235–240 (1995).
  • Rossi L , SquittiR, CalabreseL, RotilioG, RossiniPM. Alteration of peripheral markers of copper homeostasis in Alzheimer‘s disease patients: implications in aetiology and therapy. J. Nutr. Health Aging11(5), 408–417 (2007).
  • Squitti R , LupoiD, PasqualettiPet al. Elevation of serum copper levels in Alzheimer‘s disease. Neurology 59(8), 1153–1161 (2002).
  • Bucossi S , VentrigliaM, PanettaVet al. Copper in Alzheimer‘s disease: a meta-analysis of serum, plasma, and cerebrospinal fluid studies. J. Alzheimers Dis. 24(1), 175–185 (2011).
  • Brewer GJ , KanzerSH, ZimmermanEA, CelminsDF, HeckmanSM, DickR. Copper and ceruloplasmin abnormalities in Alzheimer‘s disease. Am. J. Alzheimers Dis. Other Demen.25(6), 490–497 (2010).
  • Molina JA , Jimenez-JimenezFJ, AguilarMVet al. Cerebrospinal fluid levels of transition metals in patients with Alzheimer‘s disease. J. Neural Transm. 105(4–5), 479–488 (1998).
  • Ozcankaya R , DelibasN. Malondialdehyde, superoxide dismutase, melatonin, iron, copper, and zinc blood concentrations in patients with Alzheimer disease: cross-sectional study. Croat. Med. J.43(1), 28–32 (2002).
  • Sedighi BS , M.A, ShariatiM. A study of serum copper and ceruloplasmin in Alzheimer‘s disease in Kerman, Iran. Neurology Asia11, 107–109 (2006).
  • Bocca B , ForteG, PetrucciFet al. Monitoring of chemical elements and oxidative damage in patients affected by Alzheimer‘s disease. Ann. Ist. Super. Sanita 41(2), 197–203 (2005).
  • Squitti R , PasqualettiP, CassettaEet al. Elevation of serum copper levels discriminates Alzheimer‘s disease from vascular dementia. Neurology 60(12), 2013–2014 (2003).
  • Squitti R , PasqualettiP, Dal FornoGet al. Excess of serum copper not related to ceruloplasmin in Alzheimer disease. Neurology 64(6), 1040–1046 (2005).
  • Squitti R , VentrigliaM, BarbatiGet al. ‘Free‘ copper in serum of Alzheimer‘s disease patients correlates with markers of liver function. J. Neural Transm. 114(12), 1589–1594 (2007).
  • Zappasodi F , SalustriC, BabiloniCet al. An observational study on the influence of the APOE-epsilon4 allele on the correlation between ‘free‘ copper toxicosis and EEG activity in Alzheimer disease. Brain Res. 1215, 183–189 (2008).
  • Arnal N , CristalliDO, De AlanizMJ, MarraCA. Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives. Brain Res. 1319, 118–130 (2010).
  • Rembach A , DoeckeJD, RobertsBRet al. Longitudinal analysis of serum copper and ceruloplasmin in Alzheimer‘s disease. J. Alzheimers Dis. 34(1), 171–182 (2013).
  • Maurer I , ZierzS, MollerHJ. A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiol. Aging21(3), 455–462 (2000).
  • Cottrell DA , BlakelyEL, JohnsonMA, IncePG, TurnbullDM. Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD. Neurology57(2), 260–264 (2001).
  • De Deyn PP , HiramatsuM, BorggreveFet al. Superoxide dismutase activity in cerebrospinal fluid of patients with dementia and some other neurological disorders. Alzheimer Dis. Assoc. Disord. 12(1), 26–32 (1998).
  • Omar RA , ChyanYJ, AndornAC, PoeggelerB, RobakisNK, PappollaMA. Increased expression but reduced activity of antioxidant enzymes in Alzheimer‘s disease. J. Alzheimers Dis.1(3), 139–145 (1999).
  • Milne DB , JohnsonPE. Assessment of copper status: effect of age and gender on reference ranges in healthy adults. Clin. Chem.39(5), 883–887 (1993).
  • Lewis AJ . The role of copper in inflammatory disorders. Agents Actions15(5–6), 513–519 (1984).
  • Squitti R , QuattrocchiCC, SalustriC, RossiniPM. Ceruloplasmin fragmentation is implicated in ‘free‘ copper deregulation of Alzheimer‘s disease. Prion2(1), 23–27 (2008).
  • Baum L , ChanIH, CheungSKet al. Serum zinc is decreased in Alzheimer‘s disease and serum arsenic correlates positively with cognitive ability. Biometals 23(1), 173–179 (2010).
  • Basun H , ForssellLG, WetterbergL, WinbladB. Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer‘s disease. J. Neural Transm. Park. Dis. Dement. Sect.3(4), 231–258 (1991).
  • Brewer GJ , KanzerSH, ZimmermanEAet al. Subclinical zinc deficiency in Alzheimer‘s disease and Parkinson‘s disease. Am. J. Alzheimers Dis. Other Dement. 25(7), 572–575 (2010).
  • Cornett CR , MarkesberyWR, EhmannWD. Imbalances of trace elements related to oxidative damage in Alzheimer‘s disease brain. Neurotoxicology19(3), 339–345 (1998).
  • Religa D , StrozykD, ChernyRAet al. Elevated cortical zinc in Alzheimer disease. Neurology 67(1), 69–75 (2006).
  • Ahluwalia N , GordonMA, HandteGet al. Iron status and stores decline with age in Lewis rats. J. Nutr. 130(9), 2378–2383 (2000).
  • Strozyk D , LaunerLJ, AdlardPAet al. Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid. Neurobiol. Aging 30(7), 1069–1077 (2009).
  • Mueller C , SchragM, CroftonAet al. Altered serum iron and copper homeostasis predicts cognitive decline in mild cognitive impairment. J. Alzheimers Dis. 29(2), 341–350 (2012).
  • Ferretti MT , CuelloAC. Does a pro-inflammatory process precede Alzheimer‘s disease and mild cognitive impairment?Curr. Alzheimer Res.8(2), 164–174 (2011).
  • Strang F , ScheichlA, ChenYCet al. Amyloid plaques dissociate pentameric to monomeric C-reactive protein: a novel pathomechanism driving cortical inflammation in Alzheimer‘s disease? Brain Pathol. 22(3), 337–346 (2012).
  • McGeer EG , McGeerPL. Inflammatory processes in Alzheimer‘s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry27(5), 741–749 (2003).
  • Wyss-Coray T , MuckeL. Inflammation in neurodegenerative disease–a double-edged sword. Neuron35(3), 419–432 (2002).
  • Meyer-Luehmann M , Spires-JonesTL, PradaCet al. Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer‘s disease. Nature 451(7179), 720–724 (2008).
  • Holmes C , ButchartJ. Systemic inflammation and Alzheimer‘s disease. Biochem. Soc. Trans.39(4), 898–901 (2011).
  • Schwab C , McgeerPL. Inflammatory aspects of Alzheimer disease and other neurodegenerative disorders. J. Alzheimers Dis.13(4), 359–369 (2008).
  • Walsh SR , CookEJ, GoulderF, JustinTA, KeelingNJ. Neutrophil–lymphocyte ratio as a prognostic factor in colorectal cancer. J. Surg. Oncol.91(3), 181–184 (2005).
  • Sarraf KM , BelcherE, RaevskyE, NicholsonAG, GoldstrawP, LimE. Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. J. Thorac. Cardiovasc. Surg.137(2), 425–428 (2009).
  • Kuyumcu ME , YesilY, OzturkZAet al. The evaluation of neutrophil–lymphocyte ratio in Alzheimer‘s disease. Dement. Geriat. Cogn. Disord. 34(2), 69–74 (2012).
  • Imtiaz F , ShafiqueK, MirzaSS, AyoobZ, VartP, RaoS. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int. Arch. Med.5(1), 2 (2012).
  • Leuner K , SchulzK, SchuttTet al. Peripheral mitochondrial dysfunction in Alzheimer‘s disease: focus on lymphocytes. Mol. Neurobiol. 46(1), 194–204 (2012).
  • Swardfager W , LanctotK, RothenburgL, WongA, CappellJ, HerrmannN. A meta-analysis of cytokines in Alzheimer‘s disease. Biol. Psychiatry68(10), 930–941 (2010).
  • Lee KS , ChungJH, ChoiTK, SuhSY, OhBH, HongCH. Peripheral cytokines and chemokines in Alzheimer‘s disease. Dement. Geriat. Cogn. Disord.28(4), 281–287 (2009).
  • Potempa J , KorzusE, TravisJ. The serpin superfamily of proteinase inhibitors: structure, function, and regulation. J. Biol. Chem.269(23), 15957–15960 (1994).
  • Gollin PA , KalariaRN, EikelenboomP, RozemullerA, PerryG. Alpha 1-antitrypsin and alpha 1-antichymotrypsin are in the lesions of Alzheimer‘s disease. Neuroreport3(2), 201–203 (1992).
  • Liao PC , YuL, KuoCC, LinC, KuoYM. Proteomics analysis of plasma for potential biomarkers in the diagnosis of Alzheimer‘s disease. Proteomics Clin. Appl.1(5), 506–512 (2007).
  • Sihlbom C , DavidssonP, SjogrenM, WahlundLO, NilssonCL. Structural and quantitative comparison of cerebrospinal fluid glycoproteins in Alzheimer‘s disease patients and healthy individuals. Neurochem. Res.33(7), 1332–1340 (2008).
  • Nielsen HM , MinthonL, LondosEet al. Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies. Neurology 69(16), 1569–1579 (2007).
  • Choi J , MalakowskyCA, TalentJM, ConradCC, GracyRW. Identification of oxidized plasma proteins in Alzheimer‘s disease. Biochem. Biophys. Res. Commun.293(5), 1566–1570 (2002).
  • Yu HL , ChertkowHM, BergmanH, SchipperHM. Aberrant profiles of native and oxidized glycoproteins in Alzheimer plasma. Proteomics3(11), 2240–2248 (2003).
  • Sun YX , MinthonL, WallmarkA, WarkentinS, BlennowK, JanciauskieneS. Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer‘s disease. Dement. Geriat. Cogn. Disord.16(3), 136–144 (2003).
  • Nuutinen T , SuuronenT, KauppinenA, SalminenA. Clusterin: a forgotten player in Alzheimer‘s disease. Brain Res. Rev.61(2), 89–104 (2009).
  • Kim N , HanJY, RohGSet al. Nuclear clusterin is associated with neuronal apoptosis in the developing rat brain upon ethanol exposure. Alcohol. Clin. Exp. Res. 36(1), 72–82 (2012).
  • Lambert JC , HeathS, EvenGet al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer‘s disease. Nat. Genet. 41(10), 1094–1099 (2009).
  • Seshadri S , FitzpatrickAL, IkramMAet al. Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 303(18), 1832–1840 (2010).
  • Harold D , AbrahamR, HollingworthPet al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer‘s disease. Nat. Genet. 41(10), 1088–1093 (2009).
  • Schrijvers EM , KoudstaalPJ, HofmanA, BretelerMM. Plasma clusterin and the risk of Alzheimer disease. JAMA305(13), 1322–1326 (2011).
  • Thambisetty M , SimmonsA, VelayudhanLet al. Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease. Arch. Gen. Psychiatry 67(7), 739–748 (2010).
  • Silajdzic E , MinthonL, BjorkqvistM, HanssonO. No diagnostic value of plasma clusterin in Alzheimer‘s disease. PLoS ONE7(11), e50237 (2012).
  • Hu Y , HosseiniA, KauweJSet al. Identification and validation of novel CSF biomarkers for early stages of Alzheimer‘s disease. Proteomics Clin. Appl. 1(11), 1373–1384 (2007).
  • Kalaria RN , GoldeT, KroonSN, PerryG. Serine protease inhibitor antithrombin III and its messenger RNA in the pathogenesis of Alzheimer‘s disease. Am. J. Pathol.143(3), 886–893 (1993).
  • Akiyama H , IkedaK, KondoH, McGeerPL. Thrombin accumulation in brains of patients with Alzheimer‘s disease. Neurosci. Lett.146(2), 152–154 (1992).
  • Ho GJ , SmirnovaIV, AkaabouneM, HantaiD, FestoffBW. Serine proteases and their serpin inhibitors in Alzheimer‘s disease. Biomed Pharmacother.48(7), 296–304 (1994).
  • Pike CJ , VaughanPJ, CunninghamDD, CotmanCW. Thrombin attenuates neuronal cell death and modulates astrocyte reactivity induced by beta-amyloid in vitro. J. Neurochem.66(4), 1374–1382 (1996).
  • Mhatre M , NguyenA, KashaniS, PhamT, AdesinaA, GrammasP. Thrombin, a mediator of neurotoxicity and memory impairment. Neurobiol. Aging25(6), 783–793 (2004).
  • Okazaki T , YanagisawaY, NagaiT. Analysis of the affinity of each haptoglobin polymer for hemoglobin by two-dimensional affinity electrophoresis. Clin. Chim. Acta258(2), 137–144 (1997).
  • Sadrzadeh SM , GrafE, PanterSS, HallawayPE, EatonJW. Hemoglobin. A biologic fenton reagent. J. Biol. Chem.259(23), 14354–14356 (1984).
  • Gutteridge JM . The antioxidant activity of haptoglobin towards haemoglobin-stimulated lipid peroxidation. Biochim. Biophys. Acta917(2), 219–223 (1987).
  • Abraham JD , Calvayrac-PawlowskiS, CoboSet al. Combined measurement of PEDF, haptoglobin and tau in cerebrospinal fluid improves the diagnostic discrimination between alzheimer‘s disease and other dementias. Biomarkers 16(2), 161–171 (2011).
  • Zhang R , BarkerL, PinchevDet al. Mining biomarkers in human sera using proteomic tools. Proteomics 4(1), 244–256 (2004).
  • Johnson G , BraneD, BlockWet al. Cerebrospinal fluid protein variations in common to Alzheimer‘s disease and schizophrenia. Appl. Theor. Electrophor. 3(2), 47–53 (1992).
  • Mattila KM , PirttilaT, BlennowK, WallinA, ViitanenM, FreyH. Altered blood–brain-barrier function in Alzheimer‘s disease?Acta Neurol. Scand.89(3), 192–198 (1994).
  • Brown RC , HanZ, CascioC, PapadopoulosV. Oxidative stress-mediated DHEA formation in Alzheimer‘s disease pathology. Neurobiol. Aging24(1), 57–65 (2003).
  • Rammouz G , LecanuL, AisenP, PapadopoulosV. A lead study on oxidative stress-mediated dehydroepiandrosterone formation in serum: the biochemical basis for a diagnosis of Alzheimer‘s disease. J. Alzheimers Dis.24(Suppl. 2), 5–16 (2011).
  • Taurines R , DudleyE, GrasslJet al. Proteomic research in psychiatry. J. Psychopharmacol. 25(2), 151–196 (2011).
  • Lista S , FaltracoF, PrvulovicD, HampelH. Blood and plasma-based proteomic biomarker research in Alzheimer‘s disease. Prog. Neurobiol.101–102, 1–17 (2013).
  • Cutler P , AkuffoEL, BodnarWMet al. Proteomic identification and early validation of complement 1 inhibitor and pigment epithelium-derived factor: two novel biomarkers of Alzheimer‘s disease in human plasma. Proteomics Clin. Appl. 2(4), 467–477 (2008).
  • Johnstone D , MilwardEA, BerrettaR, MoscatoP. Multivariate protein signatures of pre-clinical Alzheimer‘s disease in the Alzheimer‘s disease neuroimaging initiative (ADNI) plasma proteome dataset. PLoS ONE7(4), e34341 (2012).
  • Song F , PoljakA, SmytheGA, SachdevP. Plasma biomarkers for mild cognitive impairment and Alzheimer‘s disease. Brain Res. Rev.61(2), 69–80 (2009).
  • Kawarabayashi T , ShojiM. Plasma biomarkers of Alzheimer‘s disease. Curr. Opin. Psychiatry21(3), 260–267 (2008).
  • Ray S , BritschgiM, HerbertCet al. Classification and prediction of clinical Alzheimer‘s diagnosis based on plasma signaling proteins. Nat. Med. 13(11), 1359–1362 (2007).
  • Soares HD , ChenY, SabbaghM, RoherA, SchrijversE, BretelerM. Identifying early markers of Alzheimer‘s disease using quantitative multiplex proteomic immunoassay panels. Ann. NY Acad. Sci.1180, 56–67 (2009).
  • Marksteiner J , KemmlerG, WeissEMet al. Five out of 16 plasma signaling proteins are enhanced in plasma of patients with mild cognitive impairment and Alzheimer‘s disease. Neurobiol. Aging 32(3), 539–540 (2011).
  • Rocha de Paula M , Gómez RavettiM, BerrettaR, MoscatoP. Differences in abundances of cell-signalling proteins in blood reveal novel biomarkers for early detection of clinical Alzheimer‘s disease. PLoS ONE 6(3), e17481 (2011).
  • O‘Bryant SE , XiaoG, BarberRet al. A blood-based screening tool for Alzheimer‘s disease that spans serum and plasma: findings from TARC and ADNI. PLoS ONE 6(12), e28092 (2011).
  • Doecke JD , LawsSM, FauxNGet al. Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch. Neurol. 69(10), 1318–1325 (2012).
  • Soares HD , PotterWZ, PickeringEet al. Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease. Arch. Neurol. 69(10), 1310–1317 (2012).
  • Bazenet C , LovestoneS. Plasma biomarkers for Alzheimer‘s disease: much needed but tough to find. Biomarkers Med.6(4), 441–454 (2012).
  • Kraemer S , VaughtJD, BockCet al. From SOMAmer-based biomarker discovery to diagnostic and clinical applications: a SOMAmer-based, streamlined multiplex proteomic assay. PLoS ONE 6(10), e26332 (2011).
  • Galimberti D , GhezziL, ScarpiniE. Immunotherapy against amyloid pathology in Alzheimer‘s disease. J. Neurol. Sci. doi:10.1016/j.jns.2012.12.013 (2013) (Epub ahead of print).
  • Manzone TA , DamHQ, SoltisD, SagarVV. Blood volume analysis: a new technique and new clinical interest reinvigorate a classic study. J. Nucl. Med. Technol.35(2), 55–63; quiz 77, 79 (2007).

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