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October 12, 2009

Relationships between biomarkers in aging and dementia

W. J. Jagust, MD, S. M. Landau, PhD, L. M. Shaw, PhD, J. Q. Trojanowski, MD, PhD, R. A. Koeppe, PhD, E. M. Reiman, MD, N. L. Foster, MD, R. C. Petersen, MD, PhD, M. W. Weiner, MD, J. C. Price, PhD, C. A. Mathis, PhD, and For the Alzheimer’s Disease Neuroimaging InitiativeAuthors Info & Affiliations

October 13, 2009 issue

73 (15) 1193-1199

https://doi.org/10.1212/WNL.0b013e3181bc010c

Abstract

Background: PET imaging using [¹⁸F]fluorodeoxyglucose (FDG) and [¹¹C]Pittsburgh compound B (PIB) have been proposed as biomarkers of Alzheimer disease (AD), as have CSF measures of the 42 amino acid β-amyloid protein (Aβ_1-42) and total and phosphorylated tau (t-tau and p-tau). Relationships between biomarkers and with disease severity are incompletely understood.

Methods: Ten subjects with AD, 11 control subjects, and 34 subjects with mild cognitive impairment from the Alzheimer’s Disease Neuroimaging Initiative underwent clinical evaluation; CSF measurement of Aβ_1-42, t-tau, and p-tau; and PIB-PET and FDG-PET scanning. Data were analyzed using continuous regression and dichotomous outcomes with subjects classified as “positive” or “negative” for AD based on cutoffs established in patients with AD and controls from other cohorts.

Results: Dichotomous categorization showed substantial agreement between PIB-PET and CSF Aβ_1-42 measures (91% agreement, κ = 0.74), modest agreement between PIB-PET and p-tau (76% agreement, κ = 0.50), and minimal agreement for other comparisons (κ <0.3). Mini-Mental State Examination score was significantly correlated with FDG-PET but not with PIB-PET or CSF Aβ_1-42. Regression models adjusted for diagnosis showed that PIB-PET was significantly correlated with Aβ_1-42, t-tau, and p-tau_181p, whereas FDG-PET was correlated only with Aβ_1-42.

Conclusions: PET and CSF biomarkers of Aβ agree with one another but are not related to cognitive impairment. [¹⁸F]fluorodeoxyglucose-PET is modestly related to other biomarkers but is better related to cognition. Different biomarkers for Alzheimer disease provide different information from one another that is likely to be complementary.

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Information & Authors

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Published In

Neurology^®

Volume 73 • Number 15 • October 13, 2009

Pages: 1193-1199

PubMed: 19822868

Copyright

© 2009.

Publication History

Published online: October 12, 2009

Published in print: October 13, 2009

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Authors

Affiliations & Disclosures

W. J. Jagust, MD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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S. M. Landau, PhD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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L. M. Shaw, PhD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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J. Q. Trojanowski, MD, PhD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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R. A. Koeppe, PhD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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E. M. Reiman, MD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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N. L. Foster, MD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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R. C. Petersen, MD, PhD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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M. W. Weiner, MD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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J. C. Price, PhD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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C. A. Mathis, PhD

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

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For the Alzheimer’s Disease Neuroimaging Initiative

From the Helen Wills Neuroscience Institute (W.J.J., S.M.L.), University of California Berkeley and Lawrence Berkeley National Laboratory, CA; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Nuclear Medicine (R.A.K.), Department of Radiology, University of Michigan, Ann Arbor, MI; Banner Alzheimer’s Institute and Banner Good Samaritan PET Center (E.M.R.), Phoenix, AZ; Center for Alzheimer’s Care, Imaging and Research and Department of Neurology (N.L.F.), University of Utah, Salt Lake City, UT; Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA; and Department of Radiology (J.C.P., C.A.M.), University of Pittsburgh, PA.

Notes

Address correspondence and reprint requests to Dr. William Jagust, Helen Wills Neuroscience Institute, 132 Barker Hall, University of California, Berkeley, CA 94620 [email protected]

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