MAPT and early-onset autosomal dominant Alzheimer disease: Abnormally phosphorylated pretangle tau appears to be the earliest sign leading to Alzheimer’s disease.4 Recent research suggests that soluble pretangle tau, including oligomers, is more toxic than NFT,3,5,6 while animal studies suggest that NFT is not causal for cognitive decline or neuronal death and, in some cases, may even be neuroprotective.6,7