Alzheimer's disease is both an amyloidosis and a tauopathy; its symptoms are produced by some combination of the presence of solid deposits of misfolded amyloid-β and tau protein, though there is much debate over which is more important and how they interact with one another and brain cells in order to produce pathology. Effective treatment will probably involve removing both amyloid-β and tau aggregates from brain tissue and cerebrospinal fluid. So far the best class of approach, and the one with the most funding behind it at the present, is immunotherapy, engineering the immune system to attack and remove the unwanted waste. Even that has proven to be much harder than expected, however, and the field is littered with failed trials and promising implementations that did not translate from animal studies to human biochemistry. Only recently have human trials produced meaningful results in amyloid clearance, and earnest efforts to remove tau from the brain started later and have less funding. Still, there is progress towards immunotherapies that can clear tau, as noted here:
So far, many of the antibody drugs proposed to treat Alzheimer's disease target only the amyloid plaques. Despite the latest clinical trial that is hailed as our best chance in the quest for treating Alzheimer's, all later phase trials have failed with many causing severe side effects in the patients, such as abnormal accumulation of fluid and inflammation in the brain. One of the reasons for side effects, many speculate, is due to the antibody directing a reaction towards normal amyloid present in blood vessels or simply releasing beta-amyloid caught in the vessel wall.
The authors of the study have developed a vaccine that stimulates the production of an antibody that specifically targets pathological tau, discovering its "Achilles' heel". It is able to do this because healthy tau undergoes a series of changes to its structure forming a new region that the antibody attacks. This new region (the "Achilles' heel"), while not present in healthy tau, is present in diseased tau early on. Therefore, the antibody tackles all the different varieties of pathological tau. In addition to this important specificity, the antibody is coupled to a carrier molecule that generates a considerable immune response with the added benefit that it is not present in humans, thus avoiding the development of an immune reaction towards the body itself.
Side effects have included a local reaction at the site of injection. This skin reaction is thought to occur due to the aluminum hydroxide, an adjuvant used in vaccines to enhance the body's own antibody production. No other serious secondary effects were directly related to the vaccine. Overall, the safety of the drug and its ability to elicit an immune response were remarkable. While many trials against Alzheimer's disease stubbornly continue to target amyloid, our study dares to attack the disease from another standpoint. This is the first active vaccination to harness the body's ability to produce antibodies against pathological tau. Even though this study is only a phase 1 trial, its success so far gives the authors confidence that it may be the answer they are looking for to halt the progress of this devastating disease.
Link: https://www.eurekale...i-tfc121216.php
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