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Abstract: Recently developed positron emission tomography (PET) tracers, such as PIB and FDDNP, help to visualize amyloid plaques and neurofibrillary tangles in living subjects. FDDNP binds to both amyloid plaques and tangles, whereas PIB selectively labels amyloid plaques. Therefore, it will be interesting to see a direct comparison of the regional binding of the two radiotracers for plaques (PIB) and plaques and tangles (FDDNP) using multitracer PET imaging for both PIB and FDDNP in the same subjects with and without Alzheimer''s disease. Here we report that multitracer PET images of PIB and FDDNP in the same Alzheimer subjects show negligible PIB but strong FDDNP binding in the medial temporal cortex (hippocampus, amygdala, and parahippocampal gyrus), whereas there are significant quantities of both PIB and FDDNP binding in neocortical areas. These results suggest that tangles rather than amyloid plaques are the dominant pathology in the medial temporal cortex of living Alzheimer patients. In nondemented elderly normal subjects, PIB binding shows a significant increase in the posterior cingulate cortex compared with other brain regions, whereas in the same normal subjects we found significant FDDNP binding in the medial temporal cortex. Interestingly, the medial temporal FDDNP uptake values in normal elderly subjects were inversely correlated with long delay recall scores in the California Verbal Learning Test, a measure of episodic memory performance. We conclude that multitracer PET imaging of amyloid plaques and tangles using FDDNP and PIB in both nondemented and demented subjects provides important insight into these complicated pathological processes in living subjects. [Copyright &y& Elsevier]