Prevention and treatment of amyloidogenic disease

DETAILED DESCRIPTION I.
General Several amyloidogenic diseases and conditions are characterized by presence of deposits of A.
beta.
peptide aggregated to an insoluble mass in the brain of a patient.
Such diseases include Alzheimer's disease, Down's syndrome and cognitive impairment.
The latter is a symptom of Alzheimer's disease and Down's syndrome but can also without other characteristics of either of these diseases.
For example, mild cognitive impairment or age-associated memory loss occurs in some patient who have not yet developed, or may never develop full Alzheimer's disease.
Mild cognitive impairment can be defined by score on the Mini-Mental State Exam in accordance with convention.
Such diseases are characterized by aggregates of A.
beta.
that have a .
beta.
-pleated sheet structure and stain with Congo Red dye.
The basic approach of preventing or treating Alzheimer's disease or other amyloidogenic diseases by generating an immunogenic response to a component of the amyloid deposit in a patient is described in WO 99/27944 (incorporated by reference).
The present application reiterates and confirms the efficacy of the basic approach.
The present application is, however, principally directed to improved reagents and methods.
These improvements are premised, in part, on the present inventors having localized the preferred epitopes within A.
beta.
against which an immunogenic response should be directed.
The identification of preferred epitopes within A.
beta.
results in agents and methods having increased efficacy, reduced potential for side effects, and/or greater ease of manufacture, formulation and administration.
II.
Therapeutic Agents An immunogenic response can be active, as when an immunogen is administered to induce antibodies reactive with A.
beta.
in a patient, or passive, as when an antibody is administered that itself binds to A.
beta.
in a patient.
1.
Agents Inducing Active Immune Response Therapeutic agents induce an immunogenic response specifically directed to certain epitopes within A