Skip to main content

Advertisement

SpringerLink
Log in

Plasma levels of soluble amyloid precursor protein β in symptomatic Alzheimer’s disease

  • Short Communication
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

The established biomarkers of Alzheimer’s disease (AD) require invasive endeavours or presuppose sophisticated technical equipment. Consequently, new biomarkers are needed. Here, we report that plasma levels of soluble amyloid precursor protein β (sAPPβ), a protein of the initial phase of the amyloid cascade, were significantly lower in patients with symptomatic AD (21 with mild cognitive impairment due to AD and 44 with AD dementia) with AD-typical cerebral hypometabolic pattern compared with 27 cognitively healthy elderly individuals without preclinical AD. These findings yield further evidence for the potential of sAPPβ in plasma as an AD biomarker candidate.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Dubois B, Feldman HH, Jacova C et al (2014) Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13(6):614–629. doi:10.1016/S1474-4422(14)70090-0

    Article  PubMed  Google Scholar 

  2. McKhann GM (2011) Changing concepts of Alzheimer disease. JAMA 305(23):2458–2459. doi:10.1001/jama.2011.810

    Article  PubMed  CAS  Google Scholar 

  3. Alexopoulos P, Kurz A (2015) The new conceptualization of Alzheimer’s disease under the microscope of influential definitions of disease. Psychopathology 48(6):359–367. doi:10.1159/000441327

    Article  PubMed  Google Scholar 

  4. Martins-de-Souza D (2010) Is the word ‘biomarker’ being properly used by proteomics research in neuroscience? Eur Arch Psychiatry Clin Neurosci 260(7):561–562. doi:10.1007/s00406-010-0105-2

    Article  PubMed  PubMed Central  Google Scholar 

  5. Herukka S-K, Simonsen AH, Andreasen N et al (2017) Recommendations for cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic evaluation of mild cognitive impairment. Alzheimer’s Dement 13(3):285–295. doi:10.1016/j.jalz.2016.09.009

    Article  Google Scholar 

  6. Simonsen AH, Herukka S-K, Andreasen N et al (2017) Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia. Alzheimer’s Dement 13(3):274–284. doi:10.1016/j.jalz.2016.09.008

    Article  Google Scholar 

  7. Plassman BL, Khachaturian AS, Townsend JJ et al (2006) Comparison of clinical and neuropathologic diagnoses of Alzheimer’s disease in 3 epidemiologic samples. Alzheimer’s Dement 2(1):2–11. doi:10.1016/j.jalz.2005.11.001

    Article  Google Scholar 

  8. Weiner MW, Veitch DP, Aisen PS et al (2017) Recent publications from the Alzheimer’s disease neuroimaging initiative: reviewing progress toward improved AD clinical trials. Alzheimer’s Dement. doi:10.1016/j.jalz.2016.11.007

    Article  Google Scholar 

  9. Skillbäck T, Farahmand BY, Rosén C et al (2015) Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia. Brain 138(9):2716–2731. doi:10.1093/brain/awv181

    Article  PubMed  Google Scholar 

  10. Alexopoulos P, Kriett L, Haller B et al (2014) Limited agreement between biomarkers of neuronal injury at different stages of Alzheimer’s disease. Alzheimer’s Dement 10(6):684–689. doi:10.1016/j.jalz.2014.03.006

    Article  Google Scholar 

  11. Alexopoulos P, Roesler J, Thierjung N et al (2015) Mapping CSF biomarker profiles onto NIA-AA guidelines for Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci. doi:10.1007/s00406-015-0628-7

    Article  PubMed  Google Scholar 

  12. McKhann GM, Knopman DS, Chertkow H et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement 7(3):263–269. doi:10.1016/j.jalz.2011.03.005

    Article  Google Scholar 

  13. Albert MS, DeKosky ST, Dickson D et al (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement 7(3):270–279. doi:10.1016/j.jalz.2011.03.008

    Article  Google Scholar 

  14. Petersen RC, Aisen P, Boeve BF et al (2013) Mild cognitive impairment due to Alzheimer disease in the community. Ann Neurol 74(2):199–208. doi:10.1002/ana.23931

    Article  PubMed  PubMed Central  Google Scholar 

  15. Perneczky R, Alexopoulos P, Kurz A (2014) Soluble amyloid precursor proteins and secretases as Alzheimer’s disease biomarkers. Trends Mol Med 20(1):8–15

    Article  PubMed  CAS  Google Scholar 

  16. Smailagic N, Vacante M, Hyde C (2015) 18F-FDG PET for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 1:CD010632. doi:10.1002/14651858.CD010632.pub2

    Article  PubMed  Google Scholar 

  17. Perneczky R, Guo LH, Kagerbauer SM et al (2013) Soluble amyloid precursor protein beta as blood-based biomarker of Alzheimer’s disease. Transl Psychiatry 3:e227. doi:10.1038/tp.2013.11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Wu G, Sankaranarayanan S, Hsieh SH-K et al (2011) Decrease in brain soluble amyloid precursor protein beta (sAPPbeta) in Alzheimer’s disease cortex. J Neurosci Res 89(6):822–832. doi:10.1002/jnr.22618

    Article  PubMed  CAS  Google Scholar 

  19. Alexopoulos P, Grimmer T, Perneczky R et al (2006) Progression to dementia in clinical subtypes of mild cognitive impairment. Dement Geriatr Cogn Disord 22(1):27–34. doi:10.1159/000093101

    Article  PubMed  CAS  Google Scholar 

  20. Perneczky R, Drzezga A, Boecker H et al (2010) Metabolic alterations associated with impaired clock drawing in Lewy body dementia. Psychiatry Res 181(2):85–89. doi:10.1016/j.pscychresns.2009.08.001

    Article  PubMed  CAS  Google Scholar 

  21. Alexopoulos P, Guo L-H, Jiang M et al (2013) Amyloid cascade and tau pathology cerebrospinal fluid markers in mild cognitive impairment with regards to Alzheimer’s disease cerebral metabolic signature. J Alzheimers Dis 36(2):401–408. doi:10.3233/JAD-122329

    Article  PubMed  CAS  Google Scholar 

  22. Jagust WJ, Landau SM, Shaw LM et al (2009) Relationships between biomarkers in aging and dementia. Neurology 73(15):1193–1199. doi:10.1212/WNL.0b013e3181bc010c

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  24. Wenham PR, Price WH, Blandell G (1991) Apolipoprotein E genotyping by one-stage PCR. Lancet (London, England) 337(8750):1158–1159

    Article  CAS  Google Scholar 

  25. Olsson B, Lautner R, Andreasson U et al (2016) CSF and blood biomarkers for the diagnosis of Alzheimer’s disease. A systematic review and meta-analysis. Lancet Neurol 15(7):673–684. doi:10.1016/S1474-4422(16)00070-3

    Article  PubMed  CAS  Google Scholar 

  26. Zhang S, Smailagic N, Hyde C et al. (2014) 11C-PIB-PET for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev (7):CD010386. doi:10.1002/14651858.CD010386.pub2

  27. Wu G, Sankaranarayanan S, Tugusheva K et al (2008) Decrease in age-adjusted cerebrospinal fluid beta-secretase activity in Alzheimer’s subjects. Clin Biochem 41(12):986–996. doi:10.1016/j.clinbiochem.2008.04.022

    Article  PubMed  CAS  Google Scholar 

  28. Kitazume S, Yoshihisa A, Yamaki T et al (2012) Soluble amyloid precursor protein 770 is released from inflamed endothelial cells and activated platelets: a novel biomarker for acute coronary syndrome. J Biol Chem 287(48):40817–40825. doi:10.1074/jbc.M112.398578

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Marksteiner J, Humpel C (2013) Platelet-derived secreted amyloid-precursor protein-beta as a marker for diagnosing Alzheimer’s disease. Curr Neurovasc Res 10(4):297–303

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Delvaux E, Bentley K, Stubbs V et al (2013) Differential processing of amyloid precursor protein in brain and in peripheral blood leukocytes. Neurobiol Aging 34(6):1680–1686. doi:10.1016/j.neurobiolaging.2012.12.004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Xiang Y, Bu X-L, Liu Y-H et al (2015) Physiological amyloid-beta clearance in the periphery and its therapeutic potential for Alzheimer’s disease. Acta Neuropathol 130(4):487–499. doi:10.1007/s00401-015-1477-1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Roher AE, Esh CL, Kokjohn TA et al (2009) Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer’s disease. Alzheimer’s Dement 5(1):18–29. doi:10.1016/j.jalz.2008.10.004

    Article  CAS  Google Scholar 

  33. Vignini A, Sartini D, Morganti S et al (2011) Platelet amyloid precursor protein isoform expression in Alzheimer’s disease: evidence for peripheral marker. Int J Immunopathol Pharmacol 24(2):529–534

    Article  PubMed  CAS  Google Scholar 

  34. Jiang S, Zhang M, Ren D et al (2003) Enhanced production of amyloid precursor protein mRNA by peripheral mononuclear blood cell in Alzheimer’s disease. American journal of medical genetics. Part B Psychiatr Genet 118B(1):99–102. doi:10.1002/ajmg.b.10067

    Article  Google Scholar 

  35. Chasseigneaux S, Allinquant B (2012) Functions of Abeta, sAPPalpha and sAPPbeta. Similarities and differences. J Neurochem 120(1):99–108. doi:10.1111/j.1471-4159.2011.07584.x

    Article  PubMed  CAS  Google Scholar 

  36. Kitazume S, Yoshihisa A, Yamaki T et al (2012) Soluble amyloid precursor protein 770 is released from inflamed endothelial cells and activated platelets: a novel biomarker for acute coronary syndrome. J Bio Chem 287(48):40817–40825. doi:10.1074/jbc.M112.398578

    Article  CAS  Google Scholar 

  37. Alexopoulos P, Roesler J, Thierjung N et al (2015) Mapping CSF biomarker profiles onto NIA-AA guidelines for Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci. doi:10.1007/s00406-015-0628-7

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Panagiotis Alexopoulos and Lena-Sophie Gleixner have contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany

    Panagiotis Alexopoulos, Lena-Sophie Gleixner, Lukas Werle, Felix Buhl, Nathalie Thierjung, Timo Grimmer & Alexander Kurz

  2. Department of Psychiatry, University Hospital of Rion, University of Patras, 26500, Patras, Greece

    Panagiotis Alexopoulos, Evangelia Giourou & Philippos Gourzis

  3. Max Planck Institute of Psychiatry, Munich, Germany

    Lukas Werle

  4. Department of Anaesthesiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany

    Simone M. Kagerbauer & Jan Martin

  5. Department of Urology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany

    Hubert Kübler

  6. Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany

    Igor Yakushev

  7. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany

    Robert Perneczky

  8. Neuroepidemiology and Ageing Research Unit, Faculty of Medicine, School of Public Health, The Imperial College of Science, Technology and Medicine, London, UK

    Robert Perneczky

  9. West London Mental Health NHS Trust, London, UK

    Robert Perneczky

  10. German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany

    Robert Perneczky

Authors
  1. Panagiotis Alexopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lena-Sophie Gleixner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lukas Werle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Felix Buhl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nathalie Thierjung
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Evangelia Giourou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Simone M. Kagerbauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Philippos Gourzis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hubert Kübler
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Timo Grimmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Igor Yakushev
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jan Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Alexander Kurz
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Robert Perneczky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Panagiotis Alexopoulos.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 26 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alexopoulos, P., Gleixner, LS., Werle, L. et al. Plasma levels of soluble amyloid precursor protein β in symptomatic Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 268, 519–524 (2018). https://doi.org/10.1007/s00406-017-0815-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-017-0815-9

Keywords

Search

Navigation