MAPT and Alzheimer disease: Our lab addressed this question using a single-copy gene insertion approach comparing wild-type tau to a phosphomimetic mutation of T231 to E mimicking the phosphorylation of an epitope that appears early in AD pathology or an acetylmimetic mutation of K274/K281 to Q that mimics an epitope found later in the disease, with the thought that this approach would allow us to identify the earliest molecular phenotypes associated with dysfunction [35].