MAPT and early-onset autosomal dominant Alzheimer disease: The main pathological hallmarks of Alzheimer's disease (AD) are extracellular amyloid-β (Aβ) plaques and intracellular tau neurofibrillary tangles (NFTs).1 Previous studies have consistently shown that compared with Aβ proteinopathy, tau proteinopathy is both spatially and temporally more strongly associated with neurodegeneration and cognitive impairment.2-4 This highlights the critical role of tau pathology in AD progression and the importance of better understanding how tau spreads throughout the brain.