Sequence of a human MAP‐2 region sharing epitopes with Alzheimer neurofibrillary tangles

Microtubule‐associated protein 2 (MAP‐2), an abundant neuronal protein, consists of a short microtubule‐binding domain and a long projection arm. MAP‐2 shares epitopes with Alzheimer neurofibrillary tangles (NFT). However, most anti‐MAP‐2 antibodies do not stain detergent‐extracted NFT, and the role of MAP‐2 in NFT formation has therefore been unclear. We have determined the sequence of a 1.7 kb partial MAP‐2 cDNA encoding at least three NFT epitopes. The epitopes are not removed by detergent extraction of tangle preparations, suggesting that they are integral components of NFT. Expression vectors containing restriction fragments of the cDNA were used to assign the epitopes to a 51‐amino‐acid region near the end of the MAP‐2 projection arm, distal to the microtubule.