Since soluble functional HDAC6 was depleted and co-aggregated with tau in AD brain, we speculate that gradual loss of HDAC6 function contributes to the accumulation of acetylated tau that we and others have commonly observed in AD brains, hence early changes in HDAC6 localization or activity may represent a pathological event that precedes tau pathogenesis. Here, MAPT is linked to Alzheimer disease.