One of the recurring themes throughout Alzheimer’s research is the search for a dominant mechanism. The field has successively focused on amyloid, tau, inflammation, mitochondrial dysfunction, vascular biology, insulin resistance, lipid metabolism, and most recently microglial state transitions. Each has generated compelling data. Each has attracted billions of dollars in investment. None has fully explained […]
Is Tau the Driver, or Simply the Best Marker of Disease Progression?
If the discussion surrounding amyloid has become polarized (as has been discussed in previous posts and is not all that controversial), the conversation around tau is rapidly moving in the opposite direction. Tau has increasingly become the mechanism that many believe finally explains Alzheimer’s disease. Unlike amyloid, tau pathology correlates closely with cognitive decline, spreads […]
When Does Amyloid Stop Mattering?
One of the assumptions that has quietly shaped Alzheimer’s drug development is that disease progression remains primarily driven by the same biological process from beginning to end. That is an understandable assumption. If amyloid accumulation initiates pathology, then continued amyloid accumulation should continue to drive disease. Remove the amyloid and the disease should slow or […]
Reconsidering Alzheimer’s Disease
Part I: Have We Been Asking the Wrong Question About Amyloid? Executive Summary Few therapeutic areas have consumed as much capital or generated as much frustration as Alzheimer’s disease. Over the past three decades, the field has largely been defined by one question: Is amyloid the correct target? Clinical failures reinforced skepticism, while recent approvals […]
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