Journal of Neurology

, Volume 260, Issue 10, pp 2642–2649 | Cite as

Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease in acute ischemic stroke patients

  • Tomohisa Nezu
  • Naohisa HosomiEmail author
  • Shiro Aoki
  • Kazushi Deguchi
  • Hisashi Masugata
  • Noriko Ichihara
  • Hideo Ohyama
  • Toshiho Ohtsuki
  • Masakazu Kohno
  • Masayasu Matsumoto
Original Communication


Alpha2-macroglobulin is a protease inhibitor that enhances procoagulant properties via the neutralization of plasmin, plasminogen activators and metalloproteinases. Additionally, alpha2-macroglobulin is thought to be involved in inflammatory reactions as a carrier protein for interleukin-6 (IL-6). The objective of this study was to evaluate the usefulness of alpha2-macroglobulin as a biomarker for cerebrovascular diseases. Patients with acute ischemic stroke (n = 159; 93 male and 66 female, 71.6 ± 10.3 years) and patients with no previous history of stroke (n = 77; 38 male and 39 female, 70.7 ± 9.5 years) were consecutively enrolled in this study. White matter lesions were assessed via the fluid-attenuated inversion recovery image of magnetic resonance images using the Fazekas classification. The serum alpha2-macroglobulin levels were measured by nephelometry. The serum alpha2-macroglobulin levels at admission in patients with acute ischemic stroke were higher than those in the control patients (230.2 ± 73.7 vs. 205.0 ± 55.8 mg/dl, p = 0.009). The serum alpha2-macroglobulin levels were positively correlated with age and the severity of the white matter lesions (R 2 = 0.048, p < 0.001 and R 2 = 0.058, p < 0.001, respectively), although there was no significant association between serum alpha2-macroglobulin levels and IL-6 levels. In addition, multivariate analysis showed that increased serum alpha2-macroglobulin levels were independently associated with the severity of white matter lesions [standardized partial regression coefficient (β) 0.102, p = 0.026]. Increased serum alpha2-macroglobulin levels might be involved in the pathophysiology of acute ischemic stroke. Furthermore, serum alpha2-macroglobulin levels, which were associated with high-grade white matter lesions, may reflect the chronic pathophysiological condition of cerebral small vessel disease.


Neurology Biological markers Stroke Inflammation Leukoaraiosis 



We would like to express our gratitude to Kobayashi, Furuno, Sasanishi and Hironaka for their technical assistance. This study was supported in part by research grants from the Smoking Research Foundation, the Tsuchiya Foundation, the Japan Science and Technology Agency and the Japan Heart Foundation.

Conflicts of interest



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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Tomohisa Nezu
    • 1
  • Naohisa Hosomi
    • 1
    • 2
    Email author
  • Shiro Aoki
    • 1
  • Kazushi Deguchi
    • 2
  • Hisashi Masugata
    • 2
  • Noriko Ichihara
    • 3
  • Hideo Ohyama
    • 4
  • Toshiho Ohtsuki
    • 1
  • Masakazu Kohno
    • 2
  • Masayasu Matsumoto
    • 1
  1. 1.Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health SciencesHiroshimaJapan
  2. 2.Department of Internal MedicineKagawa University School of MedicineKagawaJapan
  3. 3.Department of NeurologyNational Hospital Takamatsu Medical CenterKagawaJapan
  4. 4.Department of StrokologyOsaka Neurosurgical HospitalKagawaJapan

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