Doug Ethell has a clear and comparatively easily tested hypothesis on an important cause of Alzheimer’s disease: that it results from the progressive failure of drainage of cerebrospinal fluid through one particularly crucial pathway in the skull. This traps ever greater levels of metabolic waste in the brain, such as amyloid-β, tau, and α-synuclein, and leads to the spectrum of well-known neurodegenerative diseases characterized by protein aggregates and resultant dysfunction and death of neurons.
Dave Gobel of the Methuselah Foundation backed the first work on this hypothesis a few years back, and the result is Leucadia Therapeutics, a company now well on the way to proving that restored drainage of cerebrospinal fluid can be a basis for treatment. Along the way, supporting evidence for the important of impaired cerebrospinal fluid flow in neurodegeneration has emerged from groups studying the glymphatic system in the brain. Given that the cost of this exercise is a tiny fraction of the funding put into the development of any one anti-amyloid immunotherapy, and it should impact all forms of metabolic waste in the brain, not just one, it seems like a good path forward.