Our findings show that the tissue levels of dynactin-P50 and synaptophysin are lower in Alzheimer patients with APOE ε 4,4 compared to APOE ε 3,3, while hyperphosphorylated tau is elevated, suggesting that inheritance of ε3,3 confers a measure of neuronal resilience, even in the presence of Alzheimer's disease. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.