PET of brain amyloid and tau in mild cognitive impairment.
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.
Small
Gary W
GW
Department of Psychiatry and Biobehavioral Sciences and the Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, USA. gsmall@mednet.ucla.edu
Kepe
Vladimir
V
Ercoli
Linda M
LM
Siddarth
Prabha
P
Bookheimer
Susan Y
SY
Miller
Karen J
KJ
Lavretsky
Helen
H
Burggren
Alison C
AC
Cole
Greg M
GM
Vinters
Harry V
HV
Thompson
Paul M
PM
Huang
S-C
SC
Satyamurthy
N
N
Phelps
Michael E
ME
Barrio
Jorge R
JR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000000981:diagnostic imaging*; D009570:Nitriles / Q000378:metabolism; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D016875:tau Proteins
C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; D016229:Amyloid beta-Peptides; D009570:Nitriles; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18