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August 7, 2006

[11C]PIB in a nondemented population
Potential antecedent marker of Alzheimer disease

August 8, 2006 issue
67 (3) 446-452

Abstract

Background: Beta-amyloid (Aβ) plaques are the hallmark of Alzheimer disease (AD). A PET imaging tracer that binds to Aβ plaques in vivo, N-methyl-[11C]2-(4′-methylaminophenyl)-6-hydroxybenzothiazole (or [11C]PIB for "Pittsburgh Compound-B"), has significantly higher binding in subjects diagnosed with dementia of the Alzheimer type (DAT) compared to nondemented controls. The authors used this imaging technique to investigate whether abnormal binding occurs in clinically normal individuals, prior to the development of cognitive changes.
Methods: Forty-one nondemented subjects (age range 20 to 86 years) and 10 patients with DAT (age range 66 to 86 years) underwent [11C]PIB PET scanning. Regions of interest were drawn on the MRI over the cerebellar, prefrontal, lateral temporal, occipital, gyrus rectus, precuneus, and striatal cortex. Binding potential values (BPs), proportional to the density of [11C]PIB-Aβ binding sites, were calculated using the Logan graphical analysis and the cerebellar cortex for a reference tissue.
Results: Patients with DAT had elevated BP values vs nondemented subjects (p < 0.0001). Four of the 41 nondemented subjects had elevated cortical BP values and their BP values as a group were not significantly different from the DAT subjects' BP values. Two of these four nondemented subjects had [11C]PIB uptake, both visually and quantitatively, that was indistinguishable from the DAT subjects.
Conclusions: Elevated [11C]PIB binding in nondemented subjects suggests that [11C]PIB amyloid imaging may be sensitive for detection of a preclinical Alzheimer disease state. Longitudinal studies will be required to determine the association of elevated [11C]PIB binding and risk of developing dementia of the Alzheimer type.

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Information & Authors

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Published In

Neurology®
Volume 67Number 3August 8, 2006
Pages: 446-452
PubMed: 16894106

Publication History

Published online: August 7, 2006
Published in print: August 8, 2006

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Authors

Affiliations & Disclosures

M. A. Mintun, MD
From the Departments of Radiology (M.A.M., G.N.L., Y.I.S., C.S.D., S.Y.L., R.H.M.), Psychiatry (M.A.M., Y.I.S.), and Neurology (J.C.M.), Washington University School of Medicine, St. Louis, MO; and Departments of Psychiatry (W.E.K.), Radiology (C.A.M.), and Neurology (S.T.D.), University of Pittsburgh, PA.
G. N. LaRossa
From the Departments of Radiology (M.A.M., G.N.L., Y.I.S., C.S.D., S.Y.L., R.H.M.), Psychiatry (M.A.M., Y.I.S.), and Neurology (J.C.M.), Washington University School of Medicine, St. Louis, MO; and Departments of Psychiatry (W.E.K.), Radiology (C.A.M.), and Neurology (S.T.D.), University of Pittsburgh, PA.
Y. I. Sheline, MD
From the Departments of Radiology (M.A.M., G.N.L., Y.I.S., C.S.D., S.Y.L., R.H.M.), Psychiatry (M.A.M., Y.I.S.), and Neurology (J.C.M.), Washington University School of Medicine, St. Louis, MO; and Departments of Psychiatry (W.E.K.), Radiology (C.A.M.), and Neurology (S.T.D.), University of Pittsburgh, PA.
C. S. Dence, MS
From the Departments of Radiology (M.A.M., G.N.L., Y.I.S., C.S.D., S.Y.L., R.H.M.), Psychiatry (M.A.M., Y.I.S.), and Neurology (J.C.M.), Washington University School of Medicine, St. Louis, MO; and Departments of Psychiatry (W.E.K.), Radiology (C.A.M.), and Neurology (S.T.D.), University of Pittsburgh, PA.
S. Y. Lee, PhD
From the Departments of Radiology (M.A.M., G.N.L., Y.I.S., C.S.D., S.Y.L., R.H.M.), Psychiatry (M.A.M., Y.I.S.), and Neurology (J.C.M.), Washington University School of Medicine, St. Louis, MO; and Departments of Psychiatry (W.E.K.), Radiology (C.A.M.), and Neurology (S.T.D.), University of Pittsburgh, PA.
R. H. Mach, PhD
From the Departments of Radiology (M.A.M., G.N.L., Y.I.S., C.S.D., S.Y.L., R.H.M.), Psychiatry (M.A.M., Y.I.S.), and Neurology (J.C.M.), Washington University School of Medicine, St. Louis, MO; and Departments of Psychiatry (W.E.K.), Radiology (C.A.M.), and Neurology (S.T.D.), University of Pittsburgh, PA.
W. E. Klunk, MD, PhD
From the Departments of Radiology (M.A.M., G.N.L., Y.I.S., C.S.D., S.Y.L., R.H.M.), Psychiatry (M.A.M., Y.I.S.), and Neurology (J.C.M.), Washington University School of Medicine, St. Louis, MO; and Departments of Psychiatry (W.E.K.), Radiology (C.A.M.), and Neurology (S.T.D.), University of Pittsburgh, PA.
C. A. Mathis, PhD
From the Departments of Radiology (M.A.M., G.N.L., Y.I.S., C.S.D., S.Y.L., R.H.M.), Psychiatry (M.A.M., Y.I.S.), and Neurology (J.C.M.), Washington University School of Medicine, St. Louis, MO; and Departments of Psychiatry (W.E.K.), Radiology (C.A.M.), and Neurology (S.T.D.), University of Pittsburgh, PA.
S. T. DeKosky, MD
From the Departments of Radiology (M.A.M., G.N.L., Y.I.S., C.S.D., S.Y.L., R.H.M.), Psychiatry (M.A.M., Y.I.S.), and Neurology (J.C.M.), Washington University School of Medicine, St. Louis, MO; and Departments of Psychiatry (W.E.K.), Radiology (C.A.M.), and Neurology (S.T.D.), University of Pittsburgh, PA.
J. C. Morris, MD
From the Departments of Radiology (M.A.M., G.N.L., Y.I.S., C.S.D., S.Y.L., R.H.M.), Psychiatry (M.A.M., Y.I.S.), and Neurology (J.C.M.), Washington University School of Medicine, St. Louis, MO; and Departments of Psychiatry (W.E.K.), Radiology (C.A.M.), and Neurology (S.T.D.), University of Pittsburgh, PA.

Notes

Address correspondence and reprint requests to Dr. Mark A. Mintun, Mallinckrodt Institute of Radiology, Box 8225, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO 63110; e-mail: [email protected]

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