Development of new screening system for Alzheimer disease, in vitro Abeta sink assay, to identify the dissociation of soluble Abeta from fibrils.
Abeta is one of the primary therapeutic targets for Alzheimer disease (AD). Abeta vaccination induces the disappearance of Abeta deposits. Since few reports have focused on the reverse phase of Abeta aggregation, we established a new screening system, the in vitro Abeta sink assay, to clarify the process of dissociation of soluble forms from fibrils. Abeta42 was more resistant to dissociation from fibrils to monomers and/or low molecular weight (LMW) soluble oligomers than Abeta40. We applied this system to find a potential therapy for AD. Ultrasound irradiation significantly enhanced the dissociation of soluble Abeta from fibrils, while ultrasound experiments also confirmed the difference between Abeta40 and Abeta42. We found that some compounds enhanced the dissociation of Abeta from fibrils. Here, we proposed that Abeta42 was more resistant to dissociation from fibrils to monomers and/or LMW soluble oligomers than Abeta40, and this system might be useful to identify dissociation of soluble Abeta from fibrils.
Sato
Naoyuki
N
Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Okochi
Masayasu
M
Taniyama
Yoshiaki
Y
Kurinami
Hitomi
H
Shimamura
Munehisa
M
Takeuchi
Daisuke
D
Hamada
Hizuki
H
Fukumori
Akio
A
Kiyosue
Kazuyuki
K
Taguchi
Takahisa
T
Tanaka
Toshiyuki
T
Miyasaka
Masayuki
M
Takeda
Masatoshi
M
Ogihara
Toshio
T
Morishita
Ryuichi
R
D000544:Alzheimer Disease; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D015153:Blotting, Western; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000737:chemistry*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments