Alzheimer’s Failures Refocus Research

Alzheimer's dementia, the most common progressive brain disorder in adults, is usually described as a condition in which an abnormal protein, beta amyloid, is produced and then gums up the brain’s memory system.

Millions of dollars have been spent trying to develop a drug to attack the toxic beta amyloid. Hopes were high that tramiprosate (Alzhemed) would be that wonder drug, and it showed promise in early trials. The drug blocks or retards the production of beta amyloid. But to get approval to sell a drug in the US, it must pass a Phase 3 trial. Tramiprosate failed. It was no better than already established treatments. The pharmaceutical company stopped further development and the drug will not reach the market—at least, not as a treatment for Alzheimer's. It may be available as a nutritional supplement, but could not be labeled as treatment for any condition.

Besides drugs, another potential avenue for treatment is immunization. If the body could be made to react against beta amyloid, the protein might be removed by natural immunologic processes, much as bacteria are removed by antibodies. Indeed, active immunization—shots that made the body react against beta amyloid—have been successful in removing the amyloid. Unfortunately, a large number of people getting the shots developed brain inflammation, and many died. That halted the development of the test product.

Among experimental subjects who survived, some came to autopsy. It appeared that the immunization worked as expected in removing beta amyloid, but, unfortunately, the subjects still had dementia. In other words, removing the amyloid did not cure the dementia.

The failure of these two treatment approaches, both aimed at reducing amyloid, raises the question, how important is beta amyloid in causing Alzheimer's? It seems that reducing amyloid had little effect on the dementia in the experimental subjects. Doesn’t that mean something else is the real villain? There are other candidates for that role. Shouldn’t all efforts now be focused on them?

On the other hand, many warn that casting away the idea that beta amyloid is the culprit is way too premature. Other studies support the amyloid hypothesis, and there are certain weaknesses in the drug and vaccination experiments. It may be that both approaches, the drug and the vaccination, were started too late; either might be effective if started earlier, some scientists argue.