Relationship between microtubule-binding repeats and morphology of neurofibrillary tangle in Alzheimer's disease

Objective – The present study was performed to compare the distributions of three‐repeat (3R) and four‐repeat (4R) neurofibrillary tangles (NFT) with those of pretangles (p‐NFT), intracellular NFT (i‐NFT), and extracellular NFT (e‐NFT) in the hippocampus of Alzheimer's disease brains. Methods – NFT labeling was performed using anti‐tau antibodies: pSer262 for p‐NFT, pSer422 for i‐NFT, AT8 for e‐NFT, RD3 for 3R, and RD4 for 4R tau, and Gallyas impregnation for the NFT population. RD4‐ and pSer422‐positive NFT were detected predominantly in sectors from CA2 to CA4, while RD3‐ and pSer262‐positive NFT were predominantly present in CA1, the entorhinal cortex, and the subiculum. The tau epitope recognized by pSer262 belongs to 4R tau but it showed a strong correlation with RD3‐ and AT8‐positive NFT. Conclusions – Sectors CA2–CA4 showed predominantly 4R‐NFT containing the pSer422 epitope. pSer262 may detect the process of transformation from p‐NFT to i‐NFT, and e‐NFT consisted predominantly of 3R tau.