Transgenic Research

, Volume 28, Issue 5–6, pp 499–508 | Cite as

Serum amyloid A1 is involved in amyloid plaque aggregation and memory decline in amyloid beta abundant condition

  • Soyoung Jang
  • Woo Young Jang
  • Minjee Choi
  • Jinhee Lee
  • Wookbong Kwon
  • Junkoo Yi
  • Si Jun Park
  • Duhak Yoon
  • Sanggyu Lee
  • Myoung Ok Kim
  • Zae Young RyooEmail author
Original Paper


Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by cognitive impairment, progressive neurodegeneration, and amyloid-β (Aβ) lesion. In the neuronal death and disease progression, inflammation is known to play an important role. Our previous study on acute-phase protein serum amyloid A1 (SAA1) overexpressed mice showed that the liver-derived SAA1 accumulated in the brain by crossing the brain blood barrier (BBB) and trigger the depressive-like behavior on mouse. Since SAA1 involved in immune responses in other diseases, we focused on the possibility that SAA1 may exacerbate the neuronal inflammation related to Alzheimer’s disease. A APP/SAA overexpressed double transgenic mouse was generated using amyloid precursor protein overexpressed (APP)-c105 mice and SAA1 overexpressed mice to examine the function of SAA1 in Aβ abundant condition. Comparisons between APP and APP/SAA1 transgenic mice showed that SAA1 exacerbated amyloid aggregation and glial activation; which lead to the memory decline. Behavior tests also supported this result. Overall, overexpression of SAA1 intensified the neuronal inflammation in amyloid abundant condition and causes the greater memory decline compared to APP mice, which only expresses Aβ 1–42.


Serum amyloid A1 Alzheimer’s disease Amyloid beta Double transgenic Glia 



This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (No. 2016R1A2B4014686) and (No. 2017R1A2B4007888)

Supplementary material

11248_2019_166_MOESM1_ESM.jpg (63 kb)
Supplementary material 1 (JPEG 62 kb)
11248_2019_166_MOESM2_ESM.docx (11 kb)
Supplementary material 2 (DOCX 10 kb)


  1. Bach JH et al (2001) C-terminal fragment of amyloid precursor protein induces astrocytosis. J Neurochem 78(1):109–120CrossRefGoogle Scholar
  2. Badolato R et al (1994) Serum amyloid A is a chemoattractant: induction of migration, adhesion, and tissue infiltration of monocytes and polymorphonuclear leukocytes. J Exp Med 180(1):203–209CrossRefGoogle Scholar
  3. Bhak G, Choe YJ, Paik SR (2009) Mechanism of amyloidogenesis: nucleation-dependent fibrillation versus double-concerted fibrillation. BMB Rep 42(9):541–551CrossRefGoogle Scholar
  4. Chung JK et al (2016) Cortical amyloid beta deposition and current depressive symptoms in alzheimer disease and mild cognitive impairment. J Geriatr Psychiatry Neurol 29(3):149–159CrossRefGoogle Scholar
  5. Chung TF et al (2000) Serum amyloid A in Alzheimer's disease brain is predominantly localized to myelin sheaths and axonal membrane. Amyloid 7(2):105–110CrossRefGoogle Scholar
  6. Collins JM et al (2015) The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease. Exp Neurol 267:219–229CrossRefGoogle Scholar
  7. De Simone V et al (2015) Th17-type cytokines, IL-6 and TNF-alpha synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene 34(27):3493–3503CrossRefGoogle Scholar
  8. Duyckaerts C, Potier MC, Delatour B (2008) Alzheimer disease models and human neuropathology: similarities and differences. Acta Neuropathol 115(1):5–38CrossRefGoogle Scholar
  9. Fritschi SK et al (2014) Highly potent soluble amyloid-beta seeds in human Alzheimer brain but not cerebrospinal fluid. Brain 137(Pt 11):2909–2915CrossRefGoogle Scholar
  10. Gou JT et al (2002) Inflammation-dependent cerebral deposition of serum amyloid a protein in a mouse model of amyloidosis. J Neurosci 22(14):5900–5909CrossRefGoogle Scholar
  11. Han MS et al (2013) JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science 339(6116):218–222CrossRefGoogle Scholar
  12. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297(5580):353–356CrossRefGoogle Scholar
  13. Jang WY et al (2016) Overexpression of serum amyloid a 1 induces depressive-like behavior in mice. Brain ResGoogle Scholar
  14. Jang WY et al (2017) Overexpression of serum amyloid a 1 induces depressive-like behavior in mice. Brain Res 1654(Pt A):55–65CrossRefGoogle Scholar
  15. Ji YR et al (2015) Hepatic serum amyloid A1 aggravates T cell-mediated hepatitis by inducing chemokines via Toll-like receptor 2 in mice. J Biol Chem 290(20):12804–12811CrossRefGoogle Scholar
  16. Kindy MS et al (1999) Apolipoprotein serum amyloid a in alzheimer's disease. J Alzheimers Dis 1(3):155–167CrossRefGoogle Scholar
  17. Kindy MS et al (1999) Apolipoprotein serum amyloid a in Alzheimer's disease. Neuropathol Appl J Alzheimers Dis 1(3):155–167CrossRefGoogle Scholar
  18. Lesne SE et al (2013) Brain amyloid-beta oligomers in ageing and Alzheimer's disease. Brain 136(Pt 5):1383–1398CrossRefGoogle Scholar
  19. Lim HJ et al (2005) NSE-controlled carboxyl-terminus of APP gene over-expressing in transgenic mice induces altered expressions in behavior, Abeta-42, and GSK3beta binding proteins. Cell Mol Neurobiol 25(5):833–850CrossRefGoogle Scholar
  20. Parra MA et al (2015) Memory binding and white matter integrity in familial Alzheimer's disease. Brain 138(Pt 5):1355–1369CrossRefGoogle Scholar
  21. Pujadas L et al (2014) Reelin delays amyloid-beta fibril formation and rescues cognitive deficits in a model of Alzheimer's disease. Nat Commun 5:3443CrossRefGoogle Scholar
  22. Rodrigues R, Petersen RB, Perry G (2014) Parallels between major depressive disorder and Alzheimer's disease: role of oxidative stress and genetic vulnerability. Cell Mol Neurobiol 34(7):925–949CrossRefGoogle Scholar
  23. Song C et al (2009) Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes. Atherosclerosis 207(2):374–383CrossRefGoogle Scholar
  24. Storey E, Cappai R (1999) The amyloid precursor protein of Alzheimer's disease and the Abeta peptide. Neuropathol Appl Neurobiol 25(2):81–97CrossRefGoogle Scholar
  25. Suh YH, Checler F (2002) Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and pharmacological applications in Alzheimer's disease. Pharmacol Rev 54(3):469–525CrossRefGoogle Scholar
  26. Wragg RE, Jeste DV (1989) Overview of depression and psychosis in Alzheimer's disease. Am J Psychiatry 146(5):577–587CrossRefGoogle Scholar
  27. Zhang C et al (2013) Interleukin-6/signal transducer and activator of transcription 3 (STAT3) pathway is essential for macrophage infiltration and myoblast proliferation during muscle regeneration. J Biol Chem 288(3):1489–1499CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Soyoung Jang
    • 1
  • Woo Young Jang
    • 4
    • 5
  • Minjee Choi
    • 1
    • 7
  • Jinhee Lee
    • 1
  • Wookbong Kwon
    • 1
  • Junkoo Yi
    • 3
  • Si Jun Park
    • 1
  • Duhak Yoon
    • 6
  • Sanggyu Lee
    • 1
  • Myoung Ok Kim
    • 2
  • Zae Young Ryoo
    • 1
    Email author
  1. 1.School of Life Science and Biotechnology, KNU Creative BioResearch Group (BK21 Plus Project)Kyungpook National UniversityDaeguRepublic of Korea
  2. 2.School of Animal Biotechnology (BT) ScienceKyungpook National UniversityDaeguRepublic of Korea
  3. 3.Gyeongsangbukdo Livestock Institute ResearchYeongju-cityRepublic of Korea
  4. 4.Laboratory Animal Resources Division, Toxicological Evaluation and Research DepartmentNational Institute of Food and Drug Safety EvaluationCheongju-siRepublic of Korea
  5. 5.Osong Health Technology Administration ComplexCheongju-siRepublic of Korea
  6. 6.Department of Animal ScienceKyungpook National UniversityDaeguRepublic of Korea
  7. 7.Core Protein Resources CenterDGISTDaeguRepublic of Korea

Personalised recommendations