The quantitation of 14 unmodified tau peptides in brain insoluble extracts confirmed that tau species containing upstream of MTBR domain (residues 243-254: MTBR-tau-243) and repeat region 2 (R2) to R3 and R4 (residues 299-317: MTBR-tau-299 and residues 354-369: MTBR-tau-354, respectively) were specifically enriched in AD compared to Abeta+ and control cases (2- to 4-fold difference in magnitude. This evidence concerns the gene APP and Alzheimer disease.