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Pittsburgh compound B and the postmortem diagnosis of alzheimer disease

Authors

  • Dana M. Niedowicz PhD,

    1. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY
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  • Tina L. Beckett HBSc,

    1. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
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  • Sergey Matveev PhD,

    1. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY
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  • Adam M. Weidner PhD,

    1. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY
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  • Irfan Baig PhD,

    1. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY
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  • Richard J. Kryscio PhD,

    1. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Statistics, University of Kentucky, Lexington, KY
    3. Department of Biostatistics, University of Kentucky, Lexington, KY
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  • Marta S. Mendiondo PhD,

    1. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Biostatistics, University of Kentucky, Lexington, KY
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  • Harry LeVine III PhD,

    Corresponding author
    1. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY
    • 209 Sanders-Brown Center on Aging, 800 S. Limestone, Lexington, KY 40536-0230
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  • Jeffrey N. Keller PhD,

    Corresponding author
    1. Pennington Biomedical Research Center/Louisiana State University System, Baton Rouge, LA
    • Pennington Biomedical Research Center/LSU System, 6400 Perkins Road, Baton Rouge, LA 70808-4124
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  • M.Paul Murphy PhD

    Corresponding author
    1. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
    2. Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY
    3. Center for Muscle Biology, University of Kentucky, Lexington, KY
    • 211 Sanders-Brown Center on Aging, 800 S. Limestone, Lexington, KY 40536-0230
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Abstract

Objective:

Deposition of the amyloid-β (Aβ) peptide in neuritic plaques is a requirement for the diagnosis of Alzheimer disease (AD). Although the continued development of in vivo imaging agents such as Pittsburgh compound B (PiB) is promising, the diagnosis of AD is still challenging. This can be partially attributed to our lack of a detailed understanding of the interrelationship between the various pools and species of Aβ and other common indices of AD pathology. We hypothesized that recent advances in our ability to accurately measure Aβ postmortem (for example, using PiB), could form the basis of a simple means to deliver an accurate AD diagnosis.

Methods:

We conducted a comprehensive analysis of the amount of Aβ40 and Aβ42 in increasingly insoluble fractions, oligomeric Aβ, and fibrillar Aβ (as defined by PiB binding), as well as plaques (diffuse and neuritic), and neurofibrillary tangles in autopsy specimens from age-matched, cognitively normal controls (n = 23) and AD (n = 22) cases, across multiple brain regions.

Results:

Both PiB binding and the amount of sodium dodecyl sulfate (SDS)-soluble Aβ were able to predict disease status; however, SDS-soluble Aβ was a better measure. Oligomeric Aβ was not a predictor of disease status. PiB binding was strongly related to plaque count, although diffuse plaques were a stronger correlate than neuritic plaques.

Interpretation:

Although postmortem PiB binding was somewhat useful in distinguishing AD from control cases, SDS-soluble Aβ measured by standard immunoassay was substantially better. These findings have important implications for the development of imaging-based biomarkers of AD. ANN NEUROL 2012;72:564–570

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