SOMATODENDRITIC LOCALIZATION AND HYPERPHOSPHORYLATION OF TAU-PROTEIN IN TRANSGENIC MICE EXPRESSING THE LONGEST HUMAN BRAIN TAU-ISOFORM

Microtubule-associated protein tau is the major constituent of the pai red helical filament, the main fibrous component of the neurofibrillar y lesions of Alzheimer's disease. Tau is an axonal phosphoprotein in n ormal adult brain. In Alzheimer's disease brain tau is hyperphosphoryl ated and is found not only in axons, but also in cell bodies and dendr ites of affected nerve cells. We report the production and analysis of transgenic mice that express the longest human brain tau isoform unde r the control of the human Thy-1 promoter. As in Alzheimer's disease, transgenic human tau protein was present in nerve cell bodies, axons a nd dendrites; moreover, it was phosphorylated at sites that are hyperp hosphorylated in paired helical filaments. We conclude that transgenic human tau protein showed pre-tangle changes similar to those that pre cede the full neurofibrillary pathology in Alzheimer's disease.