PET of Brain Amyloid and Tau in Mild Cognitive Impairment
Gary W. Small, M.D., Vladimir Kepe, Ph.D., Linda M. Ercoli, Ph.D., Prabha Siddarth, Ph.D., Susan Y. Bookheimer, Ph.D., Karen J. Miller, Ph.D., Helen Lavretsky, M.D., Alison C. Burggren, Ph.D., Greg M. Cole, Ph.D., Harry V. Vinters, M.D., Paul M. Thompson, Ph.D., S.-C. Huang, Ph.D., N. Satyamurthy, Ph.D., Michael E. Phelps, Ph.D., and Jorge R. Barrio, Ph.D.
Background Amyloid senile plaques and tau neurofibrillary tanglesare neuropathological hallmarks of Alzheimer's disease thataccumulate in the cortical regions of the brain in persons withmild cognitive impairment who are at risk for Alzheimer's disease.Noninvasive methods to detect these abnormal proteins are potentiallyuseful in developing surrogate markers for drug discovery anddiagnostics.
Methods We enrolled 83 volunteers with self-reported memoryproblems who had undergone neurologic and psychiatric evaluationand positron-emission tomography (PET). On the basis of cognitivetesting, 25 volunteers were classified as having Alzheimer'sdisease, 28 as having mild cognitive impairment, and 30 as havingno cognitive impairment (healthy controls). PET was performedafter 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 thevalues for the temporal, parietal, posterior cingulate, andfrontal regions) were lower in the control group than in thegroup with mild cognitive impairment (P<0.001), and the valuesfor binding in the group with mild cognitive impairment werelower than in the group with Alzheimer's disease (P<0.001).FDDNP-PET binding differentiated among the diagnostic groupsbetter than did metabolism on FDG-PET or volume on MRI.
Conclusions FDDNP-PET scanning can differentiate persons withmild cognitive impairment from those with Alzheimer's diseaseand those with no cognitive impairment. This technique is potentiallyuseful as a noninvasive method to determine regional cerebralpatterns of amyloid plaques and tau neurofibrillary tangles.
Source Information
From the Department of Psychiatry and Biobehavioral Sciences and the Semel Institute for Neuroscience and Human Behavior (G.W.S., L.M.E., P.S., S.Y.B., K.J.M., H.L., A.C.B.), the Department of Molecular and Medical Pharmacology (V.K., S.-C.H., N.S., M.E.P., J.R.B.), the Departments of Neurology (G.M.C., P.M.T.) and Pathology and Laboratory Medicine (H.V.V.), the Brain Mapping Center (S.Y.B., A.C.B.), the Laboratory of Neuro Imaging (P.M.T.), the Alzheimer's Disease Center (G.W.S., G.M.C., H.V.V.), and the Center on Aging (G.W.S.) — all at the David Geffen School of Medicine at the University of California, Los Angeles.
Address reprint requests to Dr. Small at the Semel Institute, Suite 88-201, 760 Westwood Plaza, Los Angeles, CA 90024, or at gsmall{at}mednet.ucla.edu.
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