The folding of Tau into a paperclip-like structure, recognized by MC1 antibodies, occurs when the amino acids at residues 7–9 interact with residues 312–342, and is one of the earliest pathological alterations of Tau in Alzheimer disease, preceding the formation of neurofibrillary tangles in AD [48]. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.