Amyloid β (Aβ) toxicity has been hypothesized to initiate the pathogenesis of Alzheimer's disease (AD). The characteristic fibrillar morphology of Aβ-aggregates, that constitute the main components of senile plaque, has long been considered to account for the neurotoxicity. But recent reports argue against a primary role for mature fibrils in AD pathogenesis because of the lack of a robust correlation between the severity of neurological impairment and the extent of amyloid deposition. Toxicity from the soluble prefibrillar intermediate entity of aggregates often called oligomer has recently proposed a plausible explanation for this inconsistency. An alternative explanation is based on the observation that certain amyloid fibril morphologies are more toxic than others, indicating that not all amyloid fibrils are equally toxic. Here, we report that it is not only the β-sheeted fibrillar structure but also the surface physicochemical composition that affects the toxicity of Aβ fibrils. For the first time, colloidal gold was used to visualize by electron microscopy positive-charge clusters on Aβ fibrils. Chemical modifications as well as point-mutated Aβ synthesis techniques were applied to change the surface structures of Aβ and to show how local structure affects surface properties that are responsible for electrostatic and hydrophobic interactions with cells. We also report that covering the surface of Aβ fibers with myelin basic protein, which has surface properties contrary to those of Aβ, suppresses Aβ toxicity. On the basis of these results, we propose that the surface structure of Aβ fibrils plays an important role in Aβ toxicity.