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Apolipoprotein E and clusterin inhibit the early phase of amyloid-β aggregation in an in vitro model of cerebral amyloid angiopathy

Journal Article


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Abstract


  • Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid-β (Aβ) deposition, which leads to lobar hemorrhage and dementia. Biological molecules affecting the development of CAA have not been fully characterized. In this study, we performed proteome analysis of biopsied leptomeningeal and cortical vessels obtained from 6 CAA patients and 5 non-CAA patients who underwent surgery for large lobar hemorrhages. We found that 6 proteins, including Aβ, apolipoprotein E (apoE), clusterin (CLU), albumin, complement C4 and vitronectin were significantly upregulated in the vessels of CAA patients as compared to non-CAA patients. ApoE and CLU were found in all CAA patients. We next examined the effects of apoE and CLU on the early phase of Aβ aggregation, using a simple yet powerful in vitro model of CAA, which recapitulates the intramural periarterial drainage pathway model. We found that physiological concentrations of apoE and CLU delayed the initiation time of amyloid growth kinetics in a concentration-dependent manner. These data indicate that apoE and CLU may act as extracellular chaperones to inhibit Aβ amyloid deposition in CAA.

Authors


  •   Endo, Yoshinori (external author)
  •   Hasegawa, Kazuhiro (external author)
  •   Nomura, Ryo (external author)
  •   Arishima, Hidetaka (external author)
  •   Kikuta, Ken (external author)
  •   Yamashita, Taro (external author)
  •   Inoue, Yasuteru (external author)
  •   Ueda, Mitsuharu (external author)
  •   Ando, Yukio (external author)
  •   Mark R Wilson
  •   Hamano, Tadanori (external author)
  •   Nakamoto, Yasunari (external author)
  •   Naiki, Hironobu (external author)

Publication Date


  • 2019

Citation


  • Endo, Y., Hasegawa, K., Nomura, R., Arishima, H., Kikuta, K., Yamashita, T., Inoue, Y., Ueda, M., Ando, Y., Wilson, M. R., Hamano, T., Nakamoto, Y. & Naiki, H. (2019). Apolipoprotein E and clusterin inhibit the early phase of amyloid-β aggregation in an in vitro model of cerebral amyloid angiopathy. Acta Neuropathologica Communications, 7 (1), 1-11.

Scopus Eid


  • 2-s2.0-85060578611

Ro Full-text Url


  • https://ro.uow.edu.au/cgi/viewcontent.cgi?article=1568&context=smhpapers1

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers1/555

Number Of Pages


  • 10

Start Page


  • 1

End Page


  • 11

Volume


  • 7

Issue


  • 1

Place Of Publication


  • United Kingdom

Abstract


  • Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid-β (Aβ) deposition, which leads to lobar hemorrhage and dementia. Biological molecules affecting the development of CAA have not been fully characterized. In this study, we performed proteome analysis of biopsied leptomeningeal and cortical vessels obtained from 6 CAA patients and 5 non-CAA patients who underwent surgery for large lobar hemorrhages. We found that 6 proteins, including Aβ, apolipoprotein E (apoE), clusterin (CLU), albumin, complement C4 and vitronectin were significantly upregulated in the vessels of CAA patients as compared to non-CAA patients. ApoE and CLU were found in all CAA patients. We next examined the effects of apoE and CLU on the early phase of Aβ aggregation, using a simple yet powerful in vitro model of CAA, which recapitulates the intramural periarterial drainage pathway model. We found that physiological concentrations of apoE and CLU delayed the initiation time of amyloid growth kinetics in a concentration-dependent manner. These data indicate that apoE and CLU may act as extracellular chaperones to inhibit Aβ amyloid deposition in CAA.

Authors


  •   Endo, Yoshinori (external author)
  •   Hasegawa, Kazuhiro (external author)
  •   Nomura, Ryo (external author)
  •   Arishima, Hidetaka (external author)
  •   Kikuta, Ken (external author)
  •   Yamashita, Taro (external author)
  •   Inoue, Yasuteru (external author)
  •   Ueda, Mitsuharu (external author)
  •   Ando, Yukio (external author)
  •   Mark R Wilson
  •   Hamano, Tadanori (external author)
  •   Nakamoto, Yasunari (external author)
  •   Naiki, Hironobu (external author)

Publication Date


  • 2019

Citation


  • Endo, Y., Hasegawa, K., Nomura, R., Arishima, H., Kikuta, K., Yamashita, T., Inoue, Y., Ueda, M., Ando, Y., Wilson, M. R., Hamano, T., Nakamoto, Y. & Naiki, H. (2019). Apolipoprotein E and clusterin inhibit the early phase of amyloid-β aggregation in an in vitro model of cerebral amyloid angiopathy. Acta Neuropathologica Communications, 7 (1), 1-11.

Scopus Eid


  • 2-s2.0-85060578611

Ro Full-text Url


  • https://ro.uow.edu.au/cgi/viewcontent.cgi?article=1568&context=smhpapers1

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers1/555

Number Of Pages


  • 10

Start Page


  • 1

End Page


  • 11

Volume


  • 7

Issue


  • 1

Place Of Publication


  • United Kingdom