April 29, 2026

@michaelokun

Not so fast: Are we moving too quickly to dismiss amyloid therapies in Alzheimer’s disease? Spoiler alert: this recent Cochrane paper over-reached on its conclusions. Amyloid refers to a protein that builds up in the brain in Alzheimer’s disease and is thought to play a role in its progression. Nonino and colleagues describe in a new paper in the Cochrane Database of Systematic Reviews, an analysis of amyloid-beta-targeting monoclonal antibodies for early Alzheimer’s disease. Key Points: - Across 17 trials and over 20,000 participants, pooled antibody therapies showed little to no difference in cognition and only small effects on function at 18 months. - These therapies were associated w/ increased rates of ARIA, including brain swelling and microbleeds. - The authors conclude that removing amyloid from the brain does not appear to lead to clinically meaningful benefit. My take: Not so fast. I delayed writing about this paper until asking several colleagues to weigh in on the conclusions drawn. This is an important topic and the authors over-reached on their conclusions. The analysis pools multiple antibodies w/ very different biology, including agents that do not effectively clear amyloid. When you combine these together, you risk diluting signal and drawing mechanistic conclusions. Here are 5 points that resonated w/ me: 1- Class level pooling of biologically different antibodies may bias results toward no effect. 2- Not all amyloid therapies are the same, and whether your therapy engages the target matters. 3- The conclusion of the authors over-reaches. 4- We need to be thinking about the right drug, in the appropriately selected population. Disease stage will matter; earlier is likely better. 5- We should be careful not to prematurely redirect the field away from amyloid. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD016297/full #michaelokun #fixelinstitute #alzheimers