SERIES
Momentum for new ideas in Alzheimer’s research joined advances in neuroscience, developmental biology and origin-of-life studies to make 2022 a memorable year of biological insights.
Myriam Wares for Quanta Magazine
Introduction
Our memories are the cornerstone of our identity. Their importance is a big part of what makes Alzheimer’s disease and other forms of dementia so cruel and poignant. It’s why we’ve hoped so desperately for science to deliver a cure for Alzheimer’s, and why it is so frustrating and tragic that useful treatments have been slow to emerge. Great excitement therefore surrounded the announcement in September that a new drug, lecanemab, slowed the progression of the disease in clinical trials. If it is approved by the Food and Drug Administration, lecanemab will become only the second Alzheimer’s treatment that counteracts amyloid-beta protein, which is widely supposed to be the cause of the disease.
Yet the effects of lecanemab are so marginal that researchers debate whether the drug will really make a practical difference for patients. The fact that lecanemab stands out as a bright spot speaks to how dismal much of the history of research on treatments for Alzheimer’s has been. Meanwhile, a deeper understanding of the biology at play is fueling interest in the leading alternative theories for what causes the disease.
Speculation about how memory works is at least as old as Plato, who in one of his Socratic dialogues wrote about “the gift of Memory, the mother of the Muses,” and compared its operation to a wax stamp in the soul. We can be grateful that science has vastly improved on our understanding of memory since Plato’s time — out with the wax stamps, in with “engrams” of changes in our neurons. In this past year alone, researchers have made exciting strides toward learning how and where in the brain different aspects of our memories reside. More surprisingly, they have even found biochemical mechanisms that distinguish good memories from bad ones.
Because we are creatures with brains, we often think about memory in purely neurological terms. Yet work published early in 2022 by researchers at the California Institute of Technology suggests that even individual cells in developing tissues may carry some records of their lineage’s history. These stem cells seem to rely on that stored information when they are faced with decisions about how to specialize in response to chemical cues. Advances in biology over this past year unveiled many other surprises as well, including insights into how the brain adapts to extended food insufficiency and how migrating cells follow a path through the body. It’s worth looking back on some of the best of that work before the revelations of the coming year give us a new perspective on ourselves again.
Harol Bustos for Quanta Magazine
Introduction
A Turning Point in Alzheimer’s Research?
Many people connected to Alzheimer’s disease, either through research or through personal ties to patients, hoped that 2022 would be a banner year. Major clinical trials would finally reveal whether two new drugs addressing the perceived root cause of the disease worked. The results fell unfortunately short of expectations. One of the drugs, lecanemab, showed potential for slightly slowing the cognitive decline of some patients but was also linked to sometimes fatal side effects; the other, gantenerumab, was deemed an outright failure.
The disappointing outcomes cap three decades of research based heavily on the theory that Alzheimer’s disease is caused by plaques of amyloid proteins that build up between brain cells and kill them. Mounting evidence suggests, however, that amyloid is only one component in a much more complex disease process that involves damaging inflammation and malfunctions in how cells recycle their proteins. Most of these ideas have been around for as long as the amyloid hypothesis but are only just beginning to receive the attention they deserve.
In fact, aggregations of proteins around cells are beginning to look like an almost universal phenomenon in aging tissues and not a condition peculiar to amyloid and Alzheimer’s disease, according to work by Stanford University researchers that was announced in a preprint last spring. The observ
