Microtubule-associated protein 2: monoclonal antibodies demonstrate the selective incorporation of certain epitopes into Alzheimer neurofibrillary tangles.

Abstract

Neurofibrillary tangles (NFT) are the principal structural alteration of neuronal cell bodies in Alzheimer disease as well as in normal aging of the human brain. While the ultrastructure of these intraneuronal lesions was extensively studied, the biochemical composition of the fibers comprising the NFT is unknown. The production of 3 monoclonal antibodies against the microtubule-associated protein 2 (MAP-2), one of which intensely labels Alzheimer NFT. All 3 antibodies specifically recognize MAP-2 on immunoblots and stain brain tissue in a characteristic dendritic pattern. The 3 antibodies are directed against at least 2 different antigenic sites in the MAP-2 molecule, and 1 appears to recognize a phosphorylation site on MAP-2. That only 1 of the 3 antibodies immunolabels NFT suggests that the formation of the tangle involves some modification of the MAP-2 molecule. One aspect of Alzheimer-type neurofibrillary pathology is an aggregation of MAP-2 or MAP-2 fragments with altered neurofilamentous elements present in NFT. Normal interactive function, which putatively occurs between neurofilaments and MAP-2, may thus be disrupted in Alzheimer disease.