BACKGROUND: Amyloid senile plaques and tau neurofibrillary tangles are 
neuropathological hallmarks of Alzheimer's disease that accumulate in the 
cortical regions of the brain in persons with mild cognitive impairment who are 
at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal 
proteins are potentially useful in developing surrogate markers for drug 
discovery and diagnostics.
METHODS: We enrolled 83 volunteers with self-reported memory problems who had 
undergone neurologic and psychiatric evaluation and positron-emission tomography 
(PET). On the basis of cognitive testing, 25 volunteers were classified as 
having Alzheimer's disease, 28 as having mild cognitive impairment, and 30 as 
having no cognitive impairment (healthy controls). PET was performed after 
injection of 
2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile 
(FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects 
also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, and 72 underwent 
magnetic resonance imaging (MRI).
RESULTS: Global values for FDDNP-PET binding (average of the values for the 
temporal, parietal, posterior cingulate, and frontal regions) were lower in the 
control group than in the group with mild cognitive impairment (P<0.001), and 
the values for binding in the group with mild cognitive impairment were lower 
than in the group with Alzheimer's disease (P<0.001). FDDNP-PET binding 
differentiated among the diagnostic groups better than did metabolism on FDG-PET 
or volume on MRI.
CONCLUSIONS: FDDNP-PET scanning can differentiate persons with mild cognitive 
impairment from those with Alzheimer's disease and those with no cognitive 
impairment. This technique is potentially useful as a noninvasive method to 
determine regional cerebral patterns of amyloid plaques and tau neurofibrillary 
tangles.