The aggregation of amyloid beta-proteins (A beta) has been recognized as a key process in the pathogenesis of Alzheimer's disease (AD), so inhibiting A beta aggregation is an important strategy to prevent the onset and treatment of AD. Our recent work indicated that decreasing the positive charges (or introducing negative charges) on human lysozyme (hLys) was unfavorable in keeping the inhibiting capability of hLys on A beta aggregation. Therefore, we have herein proposed to basify hLys by conversion of the carboxyl groups into amino groups by modification with ethylene diamine. Basified hLys (Lys-B) preparations of three modification degrees (MDs), denoted as hLys-B1 (MD, 1.5), hLys-B2 (MD, 3.3), and hLys-B3 (MD, 4.4), were synthesized for modulating A beta fibrillogenesis. The hLys-B preparations kept the stability and biocompatibility as native hLys did, whereas the inhibitory potency of hLys-B on A beta fibrillogenesis increased with increasing MD. Cytotoxicity analysis showed that cell viability with 2.5 mu M hLys-B3 increased from 62.5% (with 25 mu M A beta only) to 76.1%, similar to the case with 12.5 mu M hLys (75.5%); cell viability with 6.25 mu M hLys-B3 increased to 82.0%, similar to the case with 25 mu M hLys (80.9%). The results indicate about four- to fivefold increase in the inhibition efficiency of hLys by the amino modification. Mechanistic analysis suggests that such a superior inhibitory capability of hLys-B was attributed to its more widely distributed positive charges, which promoted broad electrostatic interactions between A beta and hLys-B. Thus, hLys-B suppressed the conformational transition of A beta to beta-sheet structures at low concentrations (e.g., 2.5 mu M hLys-B3), leading to changes in the aggregation pathway and the formation of A beta species with less cytotoxicity. The findings provided new insights into the development of more potent protein-based inhibitors against A beta fibrillogenesis.