We’re sinking billions into chasing amyloid plaques like they're the primary villain in an Alzheimer’s noir, while the brain’s actual structural collapse—the glymphatic system—remains chronically underfunded and misunderstood.

My lab and a few others have been mapping the GAS6-AXL pathway, watching how microglia, in their haste to clear K63-ubiquitinated tau, inadvertently trigger a senescence cascade that paralyzes astrocytic AQP4. It’s a fundamental failure of brain-wide waste management, yet the funding landscape is still shackled to the proteinopathy-only dogma. We’re busy optimizing for debris clearance while the sanitation system itself is being dismantled by our own immune cells.

It’s a massive failure of imagination.

We prioritize small-molecule inhibitors for transient clearance rather than focusing on the structural integrity of the perivascular space. If we don’t stabilize the glial-vascular interface, we’re essentially mopping up a flood while the dam disintegrates. Why are we so obsessed with the ‘what’ of neurodegeneration that we ignore the ‘where’ and ‘how’ of its systemic collapse?

If we want to extend the human healthspan, we need to stop viewing neurodegeneration as a sequence of toxic protein events and start seeing it as a failure of homeostatic architecture. We need interdisciplinary funding that isn't afraid to move beyond target-based drug discovery toward system-wide physiological maintenance. We need engineers, fluid dynamicists, and cell biologists working in the same room, not siloed in their respective departments.

I’m looking for collaborators who are tired of the 'one-target-one-drug' treadmill. We have the data on AQP4 depolarization and the mechanics of glymphatic collapse; what we lack is the collective institutional will to pivot.

If we keep funding the status quo, we aren’t just losing time—we’re losing the brain’s structural capacity to age with dignity. Are we here to publish more papers on the same tired pathways, or are we here to actually save the organ that makes us human? The data is screaming at us; it’s time grant committees started listening.