Cerebrospinal Fluid from Alzheimer's Disease Patients Promotes Amyloid β-Protein Oligomerization

Article type: Short Communication

Authors: Ikeda, Tokuhei^a | Ono, Kenjiro^{a; b} | Elashoff, David^c | Condron, Margaret M.^b | Noguchi-Shinohara, Moeko^a | Yoshita, Mitsuhiro^a | Teplow, David B.^b | Yamada, Masahito^{a; *}

Affiliations: [a] Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan | [b] Department of Neurology, David Geffen School of Medicine; and Molecular Biology Institute and Brain Research Institute, University of California, Los Angeles, CA, USA | [c] Department of Biostatistics, University of California at Los Angeles School of Public Health, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Masahito Yamada, 13-1 Takara-machi, Kanazawa, 920-8640, Japan. Tel.: +81 76 265 2290; Fax: +81 76 234 4253; E-mail: [email protected].

Abstract: Oligomers of the amyloid β-protein (Aβ) play an important role in Alzheimer's disease (AD). We hypothesized that AD patients have a central nervous system environment that promotes Aβ oligomerization. We investigated the effect of cerebrospinal fluid (CSF) from 33 patients with AD and 33 age-matched, non-demented controls on oligomerization of Aβ1-40 and Aβ1-42 using the technique of photo-induced cross-linking of unmodified proteins. CSF inhibited oligomerization of both Aβ1-40 and Aβ1-42. This inhibitory effect was significantly weaker in AD patients than in non-demented controls. Our results indicate that AD patients have a CSF environment favorable for Aβ oligomerization.

Keywords: Alzheimer's disease, amyloid β-protein, central nervous system, oligomer, oligomerization, photo-induced cross-linking of unmodified proteins

DOI: 10.3233/JAD-2010-100075

Journal: Journal of Alzheimer's Disease, vol. 21, no. 1, pp. 81-86, 2010