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The filamentous amyloid protein aggregates found in the brain of patients affected with Alzheimer's disease principally consist of a peptide termed βA4, according to its secondary structure of β-pleated sheets and its molecular mass of about 4 kDa. It has a length of up to 42 or 43 residues. By chemical means, we have synthesized peptide analogs corresponding to the human and rodent βA4 sequences. We describe structural and functional properties of peptides spanning residues 1–43, 10–23, 1–27 and 4–27 of βA4. The peptides have been tested for their ability to form filaments in vitro. Their solubilities and secondary structures in solution and in the solid state have been used to detect differences between the properties of human and rodent βA4 sequences. We show that mouse and rat βA4 homologs are as amyloidogenic as the human sequence. The absence of amyloid deposits in the brain of aged rats and mice is therefore not due to the three amino acid substitutions identified within the sequence which is homologous to βA4 of humans. Moreover, peptides corresponding to residues 1–27 of human and rodent βA4 are solubilized under physiological conditions; thus they are very unlikely to form stable filaments in vivo. [ABSTRACT FROM AUTHOR]