Abstract: Alzheimer’s disease (AD) remains an incurable neurodegenerative disorder with devastating societal and personal impacts. Despite decades of intensive research, therapeutic efforts targeting the clinical stages of AD have largely failed to halt or reverse disease progression. This has prompted a critical shift in focus toward the earlier, preclinical stages of AD, where interventions may hold greater promise for altering the disease trajectory. Theoretical frameworks of preclinical AD, such as those proposed by Sperling et al. (2011), describe a continuum spanning over a decade or more, characterized by three progressive stages: asymptomatic amyloidosis, the onset of neurodegeneration, and subtle cognitive impairments. While this model emphasizes amyloid-β as the initiating pathology, mounting evidence challenges this amyloid-centric paradigm, positioning early tau pathology as a primary driver of early neurodegenerative changes.