Laminin inhibits A beta 40 fibril formation promoted by apolipoprotein E4 in vitro.
The aggregation of soluble A beta into insoluble amyloid fibrils is believed to be an important step in the pathogenesis of Alzheimer's disease (AD) and the prevention of this process therefore seems to be a promising strategy for the treatment of AD. Both apolipoprotein E(apoE) and laminin are known to play important roles in the regeneration of the central nervous system and both are known to accumulate in the senile plaques of the AD brains. In the present study, we therefore investigated whether or not laminin has any effect on A beta 40 fibril formation promoted by apoE4 in vitro. A thioflavine-T fluorometric assay and electron microscopic observations using negative staining together demonstrated that laminin inhibits A beta 40 fibril formation in vitro while it also inhibits A beta 40 fibril formation promoted by apoE4. These results suggested that either laminin or its derivatives may thus be effective as therapeutic agents for AD.
Monji
A
A
Department of Neuropsychiatry, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Tashiro
K
K
Yoshida
I
I
Hayashi
Y
Y
Tashiro
N
N
D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000494:pharmacology; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D005470:Fluorometry; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D051379:Mice; D008854:Microscopy, Electron; D009454:Neurofibrils / Q000502:physiology*; D013844:Thiazoles
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D007797:Laminin; D013844:Thiazoles; C009462:thioflavin T