Novel Immunotherapeutic Procedures for Prevention of Alzheimer’s Disease

There are consistent reasons why immunotherapy should work in AD [5], based on studies published during the past decade. Some of these reasons are: (a) β-amyloid plaques and their aggregated, protofibrillar and oligomeric precursors contain immunologic neo-epitopes that are absent from the full-length Amyloid Precursor Protein (APP), as well as from its soluble proteolytic derivatives restricted to the brain tissue; therefore, β-amyloid-based immunotherapies designed to selectively target pathologic neo-epitopes present on Aβ oligomers, protofibrils or fibrils, should not cause autoimmune disease in unaffected tissues throughout the organism. (b) β-amyloid buildup precedes neurodegeneration and functional loss, and the prevention of its formation or its removal can be expected to result in the slowing or the prevention of neurodegeneration. (c) β-amyloid can cause the formation of neurofibrillary tangles in vivo and in vitro, as has been supported by animal models and tissue culture. These findings strongly suggest that the removal of β-amyloid bears the potential to correct not only β-amyloid-related toxicity but also to prevent the formation of neurofibrillary tangles. (d) Conformational changes of endogenously occurring proteins and the formation of insoluble aggregates are commonly associated with neurodegeneration and brain disease, so the removal or prevention of these pathologic protein aggregates is also a therapeutic goal in the principle of immunotherapy. (e) Immunotherapy works in experimental animals and in initial clinical trials: both active immunization and passive antibody transfer consistently reduce brain β-amyloid load, improve β-amyloid-related memory impairments, and protect neurons against degeneration in many independent experiments using different mouse models and primates.