MAPT and Alzheimer disease: DCHS2 plays a role in controlling cartilage differentiation and polarity during craniofacial development32 and is associated with neurofibrillary tangle progression, a neuropathological hallmark of Alzheimer disease due to intraneuronal aggregates of highly phosphorylated microtubule-associated protein tau.33 Many SNPs in the DCHS2 region have been identified by GWAS to be associated with the age at onset of Alzheimer disease34 or with human facial feature variants such as nose columella inclination.35 However, how DCHS2 variants are involved in TPP pathogenesis remains unknown.