Distinct aggregation and toxicity of N-terminally truncated Abeta4-42 over Abeta1-42 in the presence of Zn(II)

In the brains of Alzheimer’s disease (AD) patients, the accumulation of amyloid-beta (Abeta) aggregates is found. A peptides can be truncated at the Phe4 residue in the N-terminus forming Abeta4-x peptides, which is a predominant modification observed in AD-affected brains. This modification alters Abeta’s metal-binding, aggregation, and toxicity properties. Here we report the distinct aggregation and toxicity of an N-terminally truncated Abeta, Abeta4-42, in the presence of Zn(II) with and without Abeta seeds, compared to those of full-length Abeta1-42. Our studies demonstrate that such difference between Abeta4-42 and Abeta1-42 in the presence of Zn(II) is directed by their different Zn(II)-binding properties.