Peptides corresponding to the first 40 amino acids of amyloid peptide (β1-40) and the reverse sequence (β40-1) were synthesized, purified, and compared for their ability to aggregate and cause toxicity in vitro to human neuroblastoma cells (SH-SY5Y), as well as for effects following injection into young or aged rats. Aggregation of both peptides produced similar sedimentation velocity profiles and resulted in significant toxicity in vitro with no observable differences between β1-40 and β40-1. In addition, when injected into the cortex of young rats, β1-40 was more toxic than β40-1 although both resulted in significant lesions. However, in aged rats the two peptides resulted in lesions of similar size. Alz 50 staining and abnormal neurites were associated with both β1-40 and β40-1 lesions; however, no evidence of plaques or tangles was found in either age group. While both peptides were toxic in vitro, only β1- 40 elicited Alz 50 staining of SH-SY5Y cells. Electron microscopic examination of β1-40 and β40-1 aggregates showed that β1-40 formed fibrillar structures whereas β40-1 resulted in amorphous particles. Thus, although both peptides were toxic to cultured cells and aged rats, the toxicities may have resulted from different mechanisms.
ASJC Scopus subject areas
- Developmental Neuroscience