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.
Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Naoyuki
N
Sato
Masayasu
M
Okochi
Yoshiaki
Y
Taniyama
Hitomi
H
Kurinami
Munehisa
M
Shimamura
Daisuke
D
Takeuchi
Hizuki
H
Hamada
Akio
A
Fukumori
Kazuyuki
K
Kiyosue
Takahisa
T
Taguchi
Toshiyuki
T
Tanaka
Masayuki
M
Miyasaka
Masatoshi
M
Takeda
Toshio
T
Ogihara
Ryuichi
R
Morishita
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