Journal of Neurology

, Volume 265, Issue 8, pp 1844–1849 | Cite as

Application value of serum biomarkers for choosing memantine therapy for moderate AD

  • Hong Wei
  • Xiaolan ZhuEmail author
  • Yuefeng LiEmail author
Original Communication


Although the FDA already has approved two types of drug therapies for Alzheimer’s disease, in regard to moderate AD, there is no clear research to support the best choice of drug treatment. The goal of this study was to examine the levels of serum biomarkers in moderate-AD patients and to explore the value of these serum biomarkers for the diagnosis of memantine sensitivity in AD patients who are significantly affected by MEM. In our study, 177 patients with moderate AD were enrolled and divided into memantine-sensitive AD (n = 90) and memantine-insensitive AD (n = 87) groups. The sera from all patients were collected, and seven serum biomarkers were analysed. Then, 120 patients were used to establish a diagnostic model that was built with a binary logistic regression analysis, and 57 patients were used to validate our model. In addition, the area under the receiver operating characteristic (ROC) curve was established. From the seven serum biomarkers, the four serum biomarkers that were selected in to establish the regression model were VEGF, BDNF, IL-6 and IL-1β. The ROC curve of best combined detection was 0.899. The diagnostic ratio of the logistic model was 0.825. This study suggests that the logistic regression model (LRM) and the ROC curve based on patients’ serum levels of VEGF, BDNF, IL-6 and IL-1β is a promising research for diagnosing and choosing the best course of treatment for moderate AD.


Logistic regression Alzheimer’s disease Moderate AD Memantine 



This work was supported by the Fourth Affiliated Hospital of Jiangsu University.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study procedure was approved by the ethics committee of the Fourth Affiliated Hospital of Jiangsu University, and informed consent was obtained from each participants.


  1. 1.
    Scheltens P, Blennow K, Breteler MMB et al (2016) Alzheimer’s disease. Lancet 71(834):505–517CrossRefGoogle Scholar
  2. 2.
    Burns A, Lliffe S (2009) Alzheimer’s disease. BMJ 338:b158. CrossRefPubMedGoogle Scholar
  3. 3.
    Hort J, O’Brien JT, Gainotti G et al (2010) EFNS guidelines for the diagnosis and management of Alzheimer’s disease. Eur J Neurol 17(10):1236CrossRefPubMedGoogle Scholar
  4. 4.
    Taro Kishi S, Matsunaga K, Oya et al (2017) Memantine for Alzheimer’s disease: an updated systematic review and meta-analysis. J Alzheimer’s Dis. CrossRefGoogle Scholar
  5. 5.
    Zhu G, Li J, He L et al (2015) MPTP-regulated hippocampal synaptic plasticity and memory are prevented by memantine through BDNF-TrkB pathway. Br J Pharmacol 172(9):2354–2368CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kusari J, Zhou S, Padillo E,et al (2007) Effect of memantine on neuroretinal function and retinal vascular changes of streptozotocin-induced diabetic rats. Invest Ophthalmol Visl Sci 48(11):5152CrossRefGoogle Scholar
  7. 7.
    Lai KSP, Liu CS, Rau A et al (2017) Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies. J Neurol Neurosurg Psychiatry 88:876–882CrossRefPubMedGoogle Scholar
  8. 8.
    Gu Y, Manly JJ, Mayeux RP et al (2018) An inflammation-related nutrient pattern is associated with both brain and cognitive measures in a multiethnic elderly population. Curr Alzheimer’s Res 15(5):493–501CrossRefGoogle Scholar
  9. 9.
    Alves S, Churlaud G, Audrain M et al (2017) Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer’s disease mice. Brain 140(3):826–842PubMedGoogle Scholar
  10. 10.
    Ropele S, Schmidt R, Enzinger C et al (2012) Longitudinal magnetization transfer imaging in mild to severe Alzheimer disease. Am J Neuroradiol 33:570–575CrossRefPubMedGoogle Scholar
  11. 11.
    Fujimoto H, Matsuoka T, Kato Y et al (2017) Brain regions associated with anosognosia for memory disturbance in Alzheimer’s disease: a magnetic resonance imaging study. Neuropsychiatr Dis Treat 13:1753–1759CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Trotta T, Panaro MA, Cianciulli A et al (2018) Microglia-derived extracellular vesicles in Alzheimer’s disease: a double-edged sword. Biochem Pharmacol 148:184CrossRefPubMedGoogle Scholar
  13. 13.
    Li T, Luo Z, Liu Y et al (2018) Excessive activation of NMDA receptors induced neurodevelopmental brain damage and cognitive Deficits in rats exposed to intrauterine hypoxia. Neurochem Res 43:566–580CrossRefPubMedGoogle Scholar
  14. 14.
    Rogoz Z, Skuza G, Legutko B (2008) Repeated co-treatment with fluoxetine and amantadine induces brain-derived neurotrophic factor gene expression in rats. Pharmacol Rep PR 60(6):817–26PubMedGoogle Scholar
  15. 15.
    Marvanova M, Lakso M, Pirhonen J et al (2001) The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain. Mol Cell Neurosci 18:247–58CrossRefGoogle Scholar
  16. 16.
    Jyotrimoy K, Sheila Z, Edwin P et al (2007) Effect of memantine on neuroretinal function and retinal vascular changes of streptozotocin-induced diabetic rats. Investig Ophthalmol Vis Sci 48(11):5152–5159CrossRefGoogle Scholar
  17. 17.
    Fogal B, Hewett SJ (2008) Interleukin-1β: a bridge between inflammation and excitotoxicity? J Neurochem 106(1):1–23CrossRefPubMedGoogle Scholar
  18. 18.
    Loddick SA, Rothwell NJ (1996) Neuroprotective effects of human recombinant interleukin-1 receptor antagonist in focal cerebral ischaemia in the rat. J Cereb Blood Flow Metab 16(5):932–40CrossRefPubMedGoogle Scholar
  19. 19.
    Vezzani A, Conti M, Luigi AD et al (1999) Interleukin-1β immunoreactivity and microglia are enhanced in the rat hippocampus by focal kainite application: functional evidence for enhancement of electrographic seizures. J Neurosci 19(12):5054–5065CrossRefPubMedGoogle Scholar
  20. 20.
    Lin KY, Cherng CG, Yang FR et al (2011) Memantine abolishes the formation of cocaine-induced conditioned place preference possibly via its IL-6-modulating effect in medial prefrontal cortex. Behav Brain Res 220:126–31CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Central LaboratoryThe Fourth Affiliated Hospital of Jiangsu UniversityZhenjiangPeople’s Republic of China
  2. 2.Jiangsu UniversityZhenjiangPeople’s Republic of China
  3. 3.Department of NeurologyThe Affiliated Hospital of Jiangsu UniversityZhenjiangPeople’s Republic of China
  4. 4.Department of RadiologyThe Affiliated Hospital of Jiangsu UniversityZhenjiangPeople’s Republic of China

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