Soluble Aβ homeostasis in AD and DS: Impairment of anti-amyloidogenic protection by lipoproteins

Etsuro Matsubara, Yoshiki Sekijima, Takahiko Tokuda, Katsuya Urakami, Masakuni Amari, Masami Shizuka-Ikeda, Yasushi Tomidokoro, Masaki Ikeda, Takeshi Kawarabayashi, Yasuo Harigaya, Shu Ichi Ikeda, Tetsuro Murakami, Koji Abe, Eiichi Otomo, Shunsaku Hirai, Blas Frangione, Jorge Ghiso, Mikio Shoji

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

In order to assess whether lipoproteins are physiologically able to balance and modulate the sAβ homeostasis in vivo, soluble Aβ levels in lipoprotein-depleted plasma were measured as a function of age in normal controls, Alzheimer's disease (AD) patients, and Down's syndrome (DS) cases. The reshaping of sAβ homeostasis, in particular the sAβ42-lipoprotein interaction, takes place over normal-60's, whereas mild AD patients appear to have impaired this anti-amyloidogenic mechanism resulting in a significant increase of lipoprotein-free sAβ42. Similar loss of function takes place in Down's syndrome patients. Lipoprotein-free sAβ remains significantly elevated from the pre-symptomatic through the symptomatic stages of the disease, and declines with the progression of the AD-like pathology. The dissociation of sAβ from lipoprotein-particles also occurs in brain parenchyma and the presence of soluble dimeric lipoprotein-free Aβ prior to its parenchymal deposition in AD brains would support the hypothesis that functionally declined lipoproteins may be major determinants in the production of metabolic conditions leading to higher levels of sAβ species and cerebral amyloidosis.

Original languageEnglish
Pages (from-to)833-841
Number of pages9
JournalNeurobiology of Aging
Volume25
Issue number7
DOIs
Publication statusPublished - Aug 2004

Keywords

  • Alzheimer's disease
  • Aβ dimer
  • Down's syndrome
  • Lipoprotein-free Aβ
  • sAβ homeostasis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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  • Cite this

    Matsubara, E., Sekijima, Y., Tokuda, T., Urakami, K., Amari, M., Shizuka-Ikeda, M., Tomidokoro, Y., Ikeda, M., Kawarabayashi, T., Harigaya, Y., Ikeda, S. I., Murakami, T., Abe, K., Otomo, E., Hirai, S., Frangione, B., Ghiso, J., & Shoji, M. (2004). Soluble Aβ homeostasis in AD and DS: Impairment of anti-amyloidogenic protection by lipoproteins. Neurobiology of Aging, 25(7), 833-841. https://doi.org/10.1016/j.neurobiolaging.2003.10.004