Biogen recently announced that it was abandoning its late stage drug for Alzheimer’s, aducanumab, causing investors to lose billions of dollars. They should not have been surprised. Not only have there been more than 200 failed trials for Alzheimer’s, it’s been clear for some time that researchers are likely decades away from being able to treat this dreaded disease. Which leads me to a prediction: There will be no effective therapy for Alzheimer’s disease in my lifetime. Clinically, I am an emergency physician. But my research interests include diagnostic biomarkers, which are molecular indicators of disease, and a diagnostic test for Alzheimer’s is something of a holy grail. Alzheimer’s sits right at the confluence of a number unfortunate circumstances. Stick with me on this – it’s mostly bad news for anyone middle-aged or older, but there’s a reward of sorts at the end. If you understand why there won’t be much headway on Alzheimer’s, you’ll also understand a bit more why modern medicine has been having fewer breakthroughs on major diseases. We don’t know what causes this disease For decades it was widely believed that the cause of Alzheimer’s was the build-up of abnormal proteins called amyloid and Tau. These theories dominated the field and led some to believe we were on the verge of effective treatments – through preventing or removing these abnormal proteins. But had the theories been correct we would likely have had at least one or two positive clinical trials. In retrospect, the multi-decade amyloid fixation looks like a mistake that could have been avoided. Although there is a correlation between amyloid and risk of Alzheimer’s, there are elderly people whose brains have significant amounts of the protein and yet are cognitively intact. Versions of this observation date back to at least the 1960s. That’s one reason why researchers have questioned the enthusiasm for this one hypothesis. It was always possible that the classic plaques and tangles first seen by Alois Alzheimer, and now known to be made of abnormal proteins, were epiphenomena of aging and not the cause of the disease. Epiphenomena are characteristics that are associated with the disease but are not its cause.
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