BIIB080, an antisense oligonucleotide designed to reduce tau protein production, demonstrated meaningful cognitive benefits in mild Alzheimer's patients during early-phase testing. The MAPT-targeting therapy showed dose-dependent effects on multiple cognitive assessments, with high-dose treatment groups experiencing notably slower functional deterioration compared to placebo controls. This represents a significant shift in Alzheimer's therapeutic strategy, moving beyond amyloid-focused interventions toward tau pathology—the protein tangles more directly correlated with cognitive symptoms. The tau hypothesis has gained momentum as amyloid-clearing drugs like aducanumab showed limited clinical benefit despite successfully reducing brain plaques. BIIB080's mechanism of directly suppressing tau production at the genetic level offers a more targeted approach than previous tau strategies. However, the phase 1b design prioritized safety over efficacy measurement, meaning these cognitive benefits, while encouraging, require validation in larger controlled trials. The antisense oligonucleotide platform also raises questions about long-term safety and practical delivery methods for chronic treatment. Still, these results provide compelling rationale for advancing tau-targeting therapies, potentially offering the first meaningful disease modification for the 6 million Americans living with Alzheimer's.