Transthyretin inhibition of amyloid beta aggregation and toxicity.
OBJECTIVE
The aim of this study was to investigate transthyretin (prealbumin) effects on Abeta25-35-induced cytotoxicity.


METHODS
In view of the well-recognized literature data demonstrating that Abeta25-35 fibrillar aggregates cause in vitro cytotoxicity to human red blood cells and apoptotic changes to SK-N-BE neuroblastoma cells in cultures (ultrastructural evidence), we tested transthyretin effects on these two experimental models.


RESULTS
Incubation of Abeta25-35 with transthyretin (at transthyretin concentrations equal to CSF physiological levels) demonstrated both inhibition of red blood cells lysis and neutralization of SK-N-BE neuroblastoma cells ultrastructural apoptotic changes. Moreover, transthyretin was shown to be able to inhibit the formation of fibrillar macroaggregates of Abeta25-35.


CONCLUSIONS
The findings imply that experimental systems investigating Abeta-induced cytotoxicity consider the protective interaction of transthyretin with Abeta; an interaction to be considered also in vivo in view of the fact that transthyretin immunoreactivity has been previously demonstrated in amyloid plaques of brains from Alzheimer's disease patients.
Giunta
S
S
Laboratorio Analisi Chimico-Cliniche, Microbiologiche e Diagnostica Molecolare, Ospedale Geriatrico INRCA (IRCCS), Via della Montagnola 81, 60100 Ancona, Italy. s.giunta@inrca.it
Valli
M B
MB
Galeazzi
R
R
Fattoretti
P
P
Corder
E H
EH
Galeazzi
L
L
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003224:Congo Red / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D011228:Prealbumin / Q000032:analysis / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013053:Spectrophotometry / Q000379:methods; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011228:Prealbumin; C074636:amyloid beta-protein (25-35); D003224:Congo Red