Both critics and supporters of the approval agree on the point that the antibody Aduhelm significantly reduces cerebral amyloid-ß levels. Unfortunately, this has overlooked the fact that the approach being taken with Aduhelm is based on a misconception: In the past, it was believed that Alzheimer’s disease was caused by the accumulation of amyloid-ß in the brain, and that removing the amyloid would eliminate the underlying cause of Alzheimer’s disease. However, this turned out to be false, and it is now known that amyloid-ß is part of the innate immune system response and has many protective functions, including protection against oxidative stress and its antimicrobial effect. Thus, a reduction in amyloid concentration would in no way mean that the disease process could be slowed, stopped, or even reversed. On the contrary, the brain would rather be deprived of a protective function by the antibodies. Consequently, while these drugs were promoted as “disease-reducing agents,” they turned out to be only “amyloid-reducing agents”: the amyloid is successfully reduced, but the Alzheimer’s disease is not improved; on the contrary, the dementia symptoms remain and progress.
Recently, there have already been some setbacks in antibody therapy for Alzheimer’s: most recently, the manufacturers Roche and AC had stopped the Immune 2 trials with the antibody Crenezumab after an interim analysis of the CREAD 1 and CREAD 2 trials had provided no evidence of slowing cognitive decline. Before that, Eli Lilly & Co had a disappointing setback with Solanezumab in the EXPEDITION trial, but had another antibody called Donanemab currently in regulatory approval. This also showed a significant reduction in amyloid plaques in the Phase II TRAILBLAZER-ALZ trial, but, unsurprisingly, it also failed to halt or cure the disease. Only the progression of cognitive decline could be slowed by about a third.
The study data of the antibody monotherapies are particularly disappointing when compared with the recently published clinical study of the multimodal ReCode concept according to Dr. Dale Bredesen. This therapy pursues 36 potential targets causally related to Alzheimer’s disease. The clinical study has exemplarily proven that with ReCode, through lifestyle changes, it is possible to stop or reverse the progression of Alzheimer’s disease, especially in its early stages.