Abstract: Provided herein are methods of reducing clinical decline in a subject having early Alzheimer's disease, methods of converting an amyloid positive subject having early Alzheimer's disease to amyloid negative, methods of reducing brain amyloid level in a subject, and methods of preventing Alzheimer's disease, the methods comprising administering a composition comprising a therapeutically effective amount of at least one anti-A? protofibril antibody. In some embodiments, the subject is ApoE4-positive. In some embodiments, the at least one anti-A? protofibril antibody is BAN2401.