Skip to main content

Advertisement

Log in

Protein-Based Biomarkers in Cerebrospinal Fluid and Blood for Alzheimer’s Disease

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disease. Although early diagnosis of AD is challenging, identification and treatment at the preclinical stage is critical for preventing the severe and irreversible damage to neurons. Thus, during the last few decades, many researchers have sought efficient biomarkers for early diagnosis of AD, monitoring disease progression, and gauging responses to therapies. Recently, various molecular markers have been investigated in blood, plasma, cerebrospinal fluid, and other body fluids. This review summarizes the results of some recent studies that searched for biomarkers of AD in cerebrospinal fluid (CSF) and blood.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Andreasen N et al (1999) Cerebrospinal fluid beta-amyloid(1–42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol 56(6):673–680

    CAS  PubMed  Google Scholar 

  • Andreasen N et al (2001) Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice. Arch Neurol 58(3):373–379

    CAS  PubMed  Google Scholar 

  • Armstrong PB, Quigley JP (2001) A role for protease inhibitors in immunity of long-lived animals. Adv Exp Med Biol 484:141–160

    CAS  PubMed  Google Scholar 

  • Aronson JK (2005) Biomarkers and surrogate endpoints. Br J Clin Pharmacol 59(5):491–494

    CAS  PubMed Central  PubMed  Google Scholar 

  • Assini A et al (2004) Plasma levels of amyloid beta-protein 42 are increased in women with mild cognitive impairment. Neurology 63(5):828–831

    CAS  PubMed  Google Scholar 

  • Baird DM (2006) Telomeres. Exp Gerontol 41(12):1223–1227

    CAS  PubMed  Google Scholar 

  • Barnes DE, Yaffe K (2011) The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol 10(9):819–828

    PubMed Central  PubMed  Google Scholar 

  • Bauer J et al (1991) Interleukin-6 and alpha-2-macroglobulin indicate an acute-phase state in Alzheimer’s disease cortices. FEBS Lett 285(1):111–114

    CAS  PubMed  Google Scholar 

  • Baumann M, Meri S (2004) Techniques for studying protein heterogeneity and post-translational modifications. Expert Rev Proteomics 1(2):207–217

    CAS  PubMed  Google Scholar 

  • Bibl M et al (2006) CSF diagnosis of Alzheimer’s disease and dementia with Lewy bodies. J Neural Transm 113(11):1771–1778

    CAS  PubMed  Google Scholar 

  • Blasko I et al (2005) 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

    CAS  PubMed  Google Scholar 

  • Blasko I et al (2006) Measurement of thirteen biological markers in CSF of patients with Alzheimer’s disease and other dementias. Dement Geriatr Cogn Disord 21(1):9–15

    PubMed  Google Scholar 

  • Blennow K (2004) Cerebrospinal fluid protein biomarkers for Alzheimer’s disease. NeuroRx 1(2):213–225

    PubMed Central  PubMed  Google Scholar 

  • Blennow K (2005) CSF biomarkers for Alzheimer’s disease: use in early diagnosis and evaluation of drug treatment. Expert Rev Mol Diagn 5(5):661–672

    CAS  PubMed  Google Scholar 

  • Blennow K et al (1995) Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? Mol Chem Neuropathol 26(3):231–245

    CAS  PubMed  Google Scholar 

  • Borroni B et al (2010) Blood cell markers in Alzheimer disease: amyloid precursor protein form ratio in platelets. Exp Gerontol 45(1):53–56

    CAS  PubMed  Google Scholar 

  • Britschgi M, Wyss-Coray T (2007) Systemic and acquired immune responses in Alzheimer’s disease. Int Rev Neurobiol 82:205–233

    CAS  PubMed  Google Scholar 

  • Butterfield DA (2004) Proteomics: a new approach to investigate oxidative stress in Alzheimer’s disease brain. Brain Res 1000(1–2):1–7

    CAS  PubMed  Google Scholar 

  • Cedazo-Minguez A, Winblad B (2010) Biomarkers for Alzheimer’s disease and other forms of dementia: clinical needs, limitations and future aspects. Exp Gerontol 45(1):5–14

    CAS  PubMed  Google Scholar 

  • Choi J et al (2002) Identification of oxidized plasma proteins in Alzheimer’s disease. Biochem Biophys Res Commun 293(5):1566–1570

    CAS  PubMed  Google Scholar 

  • Choi YS, Choe LH, Lee KH (2010) Recent cerebrospinal fluid biomarker studies of Alzheimer’s disease. Expert Rev Proteomics 7(6):919–929

    CAS  PubMed  Google Scholar 

  • Colciaghi F et al (2004) Platelet APP, ADAM 10 and BACE alterations in the early stages of Alzheimer disease. Neurology 62(3):498–501

    CAS  PubMed  Google Scholar 

  • Cucullo L et al (2003) Blood-brain barrier damage induces release of alpha2-macroglobulin. Mol Cell Proteomics 2(4):234–241

    CAS  PubMed  Google Scholar 

  • de la Monte SM, Wands JR (2001) Alzheimer-associated neuronal thread protein-induced apoptosis and impaired mitochondrial function in human central nervous system-derived neuronal cells. J Neuropathol Exp Neurol 60(2):195–207

    PubMed  Google Scholar 

  • De La Monte SM et al (1996) Profiles of neuronal thread protein expression in Alzheimer’s disease. J Neuropathol Exp Neurol 55(10):1038–1050

    Google Scholar 

  • Evans C et al (2012) An insight into iTRAQ: where do we stand now? Anal Bioanal Chem 404(4):1011–1027

    CAS  PubMed  Google Scholar 

  • Ewers M, Mielke MM, Hampel H (2010) Blood-based biomarkers of microvascular pathology in Alzheimer’s disease. Exp Gerontol 45(1):75–79

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fehlbaum-Beurdeley P et al (2012) Validation of AclarusDx, a blood-based transcriptomic signature for the diagnosis of Alzheimer’s disease. J Alzheimers Dis 32(1):169–181

    CAS  PubMed  Google Scholar 

  • Forman MS, Trojanowski JQ, Lee VM (2004) Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med 10(10):1055–1063

    CAS  PubMed  Google Scholar 

  • Ghanbari K, Ghanbari HA (1998) A sandwich enzyme immunoassay for measuring AD7C-NTP as an Alzheimer’s disease marker: AD7C test. J Clin Lab Anal 12(4):223–226

    CAS  PubMed  Google Scholar 

  • Ghanbari H et al (1998) Biochemical assay for AD7C-NTP in urine as an Alzheimer’s disease marker. J Clin Lab Anal 12(5):285–288

    CAS  PubMed  Google Scholar 

  • Gloeckner SF et al (2008) Quantitative analysis of transthyretin, tau and amyloid-beta in patients with dementia. J Alzheimers Dis 14(1):17–25

    CAS  PubMed  Google Scholar 

  • Goedert M (1993) Tau protein and the neurofibrillary pathology of Alzheimer’s disease. Trends Neurosci 16(11):460–465

    CAS  PubMed  Google Scholar 

  • Gorelick PB et al (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42(9):2672–2713

    PubMed Central  PubMed  Google Scholar 

  • Gygi SP et al (2000) Evaluation of two-dimensional gel electrophoresis-based proteome analysis technology. Proc Natl Acad Sci U S A 97(17):9390–9395

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hampel H, Shen Y (2009) Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) as a biological candidate marker of Alzheimer’s disease. Scand J Clin Lab Invest 69(1):8–12

    CAS  PubMed  Google Scholar 

  • Hampel H et al (2010) Total and phosphorylated tau protein as biological markers of Alzheimer’s disease. Exp Gerontol 45(1):30–40

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hansson SF et al (2009) Reduced levels of amyloid-beta-binding proteins in cerebrospinal fluid from Alzheimer’s disease patients. J Alzheimers Dis 16(2):389–397

    CAS  PubMed  Google Scholar 

  • Hebert LE et al (2003) Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 60(8):1119–1122

    PubMed  Google Scholar 

  • Hesse C et al (2000) Cerebrospinal fluid markers for Alzheimer’s disease evaluated after acute ischemic stroke. J Alzheimers Dis 2(3–4):199–206

    CAS  PubMed  Google Scholar 

  • Hu S, Jiang J, Wong DT (2010) Proteomic analysis of saliva: 2D gel electrophoresis, LC-MS/MS, and Western blotting. Methods Mol Biol 666:31–41

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hu WT et al (2012) Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease. Neurology 79(9):897–905

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hulstaert F et al (1999) Improved discrimination of AD patients using beta-amyloid(1–42) and tau levels in CSF. Neurology 52(8):1555–1562

    CAS  PubMed  Google Scholar 

  • Humpel C (2011) Identifying and validating biomarkers for Alzheimer’s disease. Trends Biotechnol 29(1):26–32

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hye A et al (2006) Proteome-based plasma biomarkers for Alzheimer’s disease. Brain 129(Pt 11):3042–3050

    CAS  PubMed  Google Scholar 

  • Irwin DJ, Trojanowski JQ, Grossman M (2013) Cerebrospinal fluid biomarkers for differentiation of frontotemporal lobar degeneration from Alzheimer’s disease. Front Aging Neurosci 5:6

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ishikawa M et al (2013) Plasma and serum from nonfasting men and women differ in their lipidomic profiles. Biol Pharm Bull 36(4):682–685

    CAS  PubMed  Google Scholar 

  • Jack CJ et al (2011) Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3):257–262

    PubMed Central  PubMed  Google Scholar 

  • Jensen M et al (1999) Cerebrospinal fluid A beta42 is increased early in sporadic Alzheimer’s disease and declines with disease progression. Ann Neurol 45(4):504–511

    CAS  PubMed  Google Scholar 

  • Kahle PJ et al (2000) Combined assessment of tau and neuronal thread protein in Alzheimer’s disease CSF. Neurology 54(7):1498–1504

    CAS  PubMed  Google Scholar 

  • Kanai M et al (1998) Longitudinal study of cerebrospinal fluid levels of tau, A beta1-40, and A beta1-42(43) in Alzheimer’s disease: a study in Japan. Ann Neurol 44(1):17–26

    CAS  PubMed  Google Scholar 

  • Kondziella D et al (2009) B-type natriuretic peptide plasma levels are elevated in subcortical vascular dementia. Neuroreport 20(9):825–827

    CAS  PubMed  Google Scholar 

  • Korolainen MA et al (2007) Multiplexed proteomic analysis of oxidation and concentrations of cerebrospinal fluid proteins in Alzheimer disease. Clin Chem 53(4):657–665

    CAS  PubMed  Google Scholar 

  • Koudinov AR et al (1998) Alzheimer’s amyloid beta interaction with normal human plasma high density lipoprotein: association with apolipoprotein and lipids. Clin Chim Acta 270(2):75–84

    CAS  PubMed  Google Scholar 

  • Lanni C et al (2007) Unfolded p53: a potential biomarker for Alzheimer’s disease. J Alzheimers Dis 12(1):93–99

    CAS  PubMed  Google Scholar 

  • Lee MS et al (2003) APP processing is regulated by cytoplasmic phosphorylation. J Cell Biol 163(1):83–95

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lewczuk P et al (2008) Multiplexed quantification of dementia biomarkers in the CSF of patients with early dementias and MCI: a multicenter study. Neurobiol Aging 29(6):812–818

    CAS  PubMed  Google Scholar 

  • Lewis TL et al (2010) Overexpression of human apolipoprotein A-I preserves cognitive function and attenuates neuroinflammation and cerebral amyloid angiopathy in a mouse model of Alzheimer disease. J Biol Chem 285(47):36958–36968

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mariani E et al (2005) Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview. J Chromatogr B Analyt Technol Biomed Life Sci 827(1):65–75

    CAS  PubMed  Google Scholar 

  • Marksteiner J, Hinterhuber H, Humpel C (2007) Cerebrospinal fluid biomarkers for diagnosis of Alzheimer’s disease: beta-amyloid(1–42), tau, phospho-tau-181 and total protein. Drugs Today (Barc) 43(6):423–431

    CAS  Google Scholar 

  • Marksteiner J et al (2011) 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

    CAS  PubMed  Google Scholar 

  • Marksteiner J et al (2014) Analysis of 27 vascular-related proteins reveals that NT-proBNP is a potential biomarker for Alzheimer’s disease and mild cognitive impairment: a pilot-study. Exp Gerontol 50:114–121

    CAS  PubMed  Google Scholar 

  • Mawuenyega KG et al (2010) Decreased clearance of CNS-amyloid in Alzheimer’s disease. Science 330(6012):1774

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mendoza-Nunez VM et al (2001) Total antioxidant levels, gender, and age as risk factors for DNA damage in lymphocytes of the elderly. Mech Ageing Dev 122(8):835–847

    CAS  PubMed  Google Scholar 

  • Merched A et al (1998) Apolipoprotein E, transthyretin and actin in the CSF of Alzheimer’s patients: relation with the senile plaques and cytoskeleton biochemistry. FEBS Lett 425(2):225–228

    CAS  PubMed  Google Scholar 

  • Mrak RE, Griffin WS (2005) Potential inflammatory biomarkers in Alzheimer’s disease. J Alzheimers Dis 8(4):369–375

    CAS  PubMed  Google Scholar 

  • Munzar M et al (2002) Clinical study of a urinary competitive ELISA for neural thread protein in Alzheimer disease. Neurol Clin Neurophysiol 2002(1):2–8

    PubMed  Google Scholar 

  • Nilselid AM et al (2006) Clusterin in cerebrospinal fluid: analysis of carbohydrates and quantification of native and glycosylated forms. Neurochem Int 48(8):718–728

    CAS  PubMed  Google Scholar 

  • Nilsson K, Gustafson L, Hultberg B (2006) Plasma homocysteine and vascular disease in psychogeriatric patients. Dement Geriatr Cogn Disord 21(3):148–154

    CAS  PubMed  Google Scholar 

  • Ong SE et al (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1(5):376–386

    CAS  PubMed  Google Scholar 

  • Otto M et al (2000) Decreased beta-amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Neurology 54(5):1099–1102

    CAS  PubMed  Google Scholar 

  • Patton RL et al (2006) Amyloid-beta peptide remnants in AN-1792-immunized Alzheimer’s disease patients: a biochemical analysis. Am J Pathol 169(3):1048–1063

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pereira C et al (2005) Alzheimer’s disease-associated neurotoxic mechanisms and neuroprotective strategies. Curr Drug Targets CNS Neurol Disord 4(4):383–403

    CAS  PubMed  Google Scholar 

  • Perrin RJ et al (2011) Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer’s disease. PLoS One 6(1):e16032

    CAS  PubMed Central  PubMed  Google Scholar 

  • Plassman BL et al (2007) Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology 29(1–2):125–132

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ponnappan U (2002) Ubiquitin-proteasome pathway is compromised in CD45RO+ and CD45RA+ T lymphocyte subsets during aging. Exp Gerontol 37(2–3):359–367

    CAS  PubMed  Google Scholar 

  • Puchades M et al (2003) Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer’s disease. Brain Res Mol Brain Res 118(1–2):140–146

    CAS  PubMed  Google Scholar 

  • Ray S et al (2007) Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nat Med 13(11):1359–1362

    CAS  PubMed  Google Scholar 

  • Riemenschneider M et al (2000) Cerebrospinal beta-amyloid ((1–42)) in early Alzheimer’s disease: association with apolipoprotein E genotype and cognitive decline. Neurosci Lett 284(1–2):85–88

    CAS  PubMed  Google Scholar 

  • Risacher SL, Saykin AJ (2013) Neuroimaging and other biomarkers for Alzheimer’s disease: the changing landscape of early detection. Annu Rev Clin Psychol 9:621–648

    PubMed Central  PubMed  Google Scholar 

  • Rodriguez DCS et al (2004) The human complement factor H: functional roles, genetic variations and disease associations. Mol Immunol 41(4):355–367

    Google Scholar 

  • Schoonenboom NS et al (2005) Amyloid beta 38, 40, and 42 species in cerebrospinal fluid: more of the same? Ann Neurol 58(1):139–142

    CAS  PubMed  Google Scholar 

  • Schraen-Maschke S et al (2008) Tau as a biomarker of neurodegenerative diseases. Biomark Med 2(4):363–384

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schuessel K et al (2004) Impact of gender on upregulation of antioxidant defence mechanisms in Alzheimer’s disease brain. J Neural Transm 111(9):1167–1182

    CAS  PubMed  Google Scholar 

  • Schultz K et al (2010) Transthyretin as a potential CSF biomarker for Alzheimer’s disease and dementia with Lewy bodies: effects of treatment with cholinesterase inhibitors. Eur J Neurol 17(3):456–460

    CAS  PubMed  Google Scholar 

  • Selkoe DJ (2004) Cell biology of protein misfolding: the examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol 6(11):1054–1061

    CAS  PubMed  Google Scholar 

  • Shaw LM et al (2009) Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol 65(4):403–413

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shih YH et al (2014) Apolipoprotein C-III is an amyloid-beta-binding protein and an early marker for Alzheimer’s disease. J Alzheimers Dis. doi:10.3233/JAD-140111

  • Sihlbom C et al (2008) Structural and quantitative comparison of cerebrospinal fluid glycoproteins in Alzheimer’s disease patients and healthy individuals. Neurochem Res 33(7):1332–1340

    CAS  PubMed  Google Scholar 

  • Sjogren M et al (2000) CSF levels of tau, beta-amyloid(1–42) and GAP-43 in frontotemporal dementia, other types of dementia and normal aging. J Neural Transm 107(5):563–579

    CAS  PubMed  Google Scholar 

  • Sjogren M et al (2001a) Low cerebrospinal fluid beta-amyloid 42 in patients with acute bacterial meningitis and normalization after treatment. Neurosci Lett 314(1–2):33–36

    CAS  PubMed  Google Scholar 

  • Sjogren M et al (2001b) Tau and Abeta42 in cerebrospinal fluid from healthy adults 21–93 years of age: establishment of reference values. Clin Chem 47(10):1776–1781

    CAS  PubMed  Google Scholar 

  • Skovronsky DM, Lee VM, Trojanowski JQ (2006) Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol 1:151–170

    CAS  PubMed  Google Scholar 

  • Soares HD et al (2009) Identifying early markers of Alzheimer’s disease using quantitative multiplex proteomic immunoassay panels. Ann N Y Acad Sci 1180:56–67

    CAS  PubMed  Google Scholar 

  • Stefani A et al (2005) AD with subcortical white matter lesions and vascular dementia: CSF markers for differential diagnosis. J Neurol Sci 237(1–2):83–88

    PubMed  Google Scholar 

  • Strauss S et al (1992) Detection of interleukin-6 and alpha 2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer’s disease patients. Lab Invest 66(2):223–230

    CAS  PubMed  Google Scholar 

  • Strohmeyer R, Shen Y, Rogers J (2000) Detection of complement alternative pathway mRNA and proteins in the Alzheimer’s disease brain. Brain Res Mol Brain Res 81(1–2):7–18

    CAS  PubMed  Google Scholar 

  • Tang K et al (2006) Platelet amyloid precursor protein processing: a bio-marker for Alzheimer’s disease. J Neurol Sci 240(1–2):53–58

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thambisetty M et al (2008) Proteome-based identification of plasma proteins associated with hippocampal metabolism in early Alzheimer’s disease. J Neurol 255(11):1712–1720

    CAS  PubMed  Google Scholar 

  • Thambisetty M et al (2010) Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease. Arch Gen Psychiatry 67(7):739

    PubMed Central  PubMed  Google Scholar 

  • Thies W, Bleiler L (2011) 2011 Alzheimer’s disease facts and figures. Alzheimers Dement 7(2):208–244

    Google Scholar 

  • Unlu M, Morgan ME, Minden JS (1997) Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis 18(11):2071–2077

    CAS  PubMed  Google Scholar 

  • Velayudhan L et al (2012) Plasma transthyretin as a candidate marker for Alzheimer’s disease. J Alzheimers Dis 28(2):369–375

    CAS  PubMed  Google Scholar 

  • Wang GP et al (1991) Brain ubiquitin is markedly elevated in Alzheimer disease. Brain Res 566(1–2):146–151

    CAS  PubMed  Google Scholar 

  • Wilson MR, Yerbury JJ, Poon S (2008) Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity. Mol Biosyst 4(1):42–52

    CAS  PubMed  Google Scholar 

  • Xu XH et al (2012) Metabolomics: a novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer’s disease. Neurosci Bull 28(5):641–648

    CAS  PubMed  Google Scholar 

  • Yerbury JJ et al (2007) The extracellular chaperone clusterin influences amyloid formation and toxicity by interacting with prefibrillar structures. FASEB J 21(10):2312–2322

    CAS  PubMed  Google Scholar 

  • Zetterberg H, Wahlund LO, Blennow K (2003) Cerebrospinal fluid markers for prediction of Alzheimer’s disease. Neurosci Lett 352(1):67–69

    CAS  PubMed  Google Scholar 

  • Zetterberg H et al (2008) Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease. Arch Neurol 65(8):1102–1107

    PubMed  Google Scholar 

  • Zetterberg H, Blennow K, Hanse E (2010) Amyloid beta and APP as biomarkers for Alzheimer’s disease. Exp Gerontol 45(1):23–29

    CAS  PubMed  Google Scholar 

  • Zhang J (2007) Proteomics of human cerebrospinal fluid—the good, the bad, and the ugly. Proteomics Clin Appl 1(8):805–819

    CAS  PubMed  Google Scholar 

  • Zhang JJ, Shi SS (2013) A literature review of AD7c-ntp as a biomarker for Alzheimer’s disease. Ann Indian Acad Neurol 16(3):307–309

    PubMed Central  PubMed  Google Scholar 

  • Zhang R et al (2004) Mining biomarkers in human sera using proteomic tools. Proteomics 4(1):244–256

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lifeng Yang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fu, Y., Zhao, D. & Yang, L. Protein-Based Biomarkers in Cerebrospinal Fluid and Blood for Alzheimer’s Disease. J Mol Neurosci 54, 739–747 (2014). https://doi.org/10.1007/s12031-014-0356-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-014-0356-x

Keyword

Navigation