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Research ArticleCLINICAL INVESTIGATIONS

Characterization of PiB Binding to White Matter in Alzheimer Disease and Other Dementias

Michelle T. Fodero-Tavoletti, Christopher C. Rowe, Catriona A. McLean, Laura Leone, Qiao-Xin Li, Colin L. Masters, Roberto Cappai and Victor L. Villemagne
Journal of Nuclear Medicine February 2009, 50 (2) 198-204; DOI: https://doi.org/10.2967/jnumed.108.057984
Michelle T. Fodero-Tavoletti
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Christopher C. Rowe
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Catriona A. McLean
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Laura Leone
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Qiao-Xin Li
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Colin L. Masters
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Roberto Cappai
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Victor L. Villemagne
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  • FIGURE 1. 
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    FIGURE 1. 

    In vitro binding studies demonstrate that 3H-PiB fails to bind to white matter brain homogenates. Scatchard plots of 3H-PiB binding to gray matter (AD patients [A] and age-matched HCs [B]) and white matter (AD patients [C] and age-matched HCs [D]) brain homogenates. Scatchard analysis indicated that 3H-PiB binds to AD gray matter (dissociation constant, 3.77 nM; maximum number of binding sites, 9,254 pmol 3H-PiB/g tissue) brain homogenates. No significant binding of 3H-PiB to HC gray matter or white matter homogenates was observed. Consequently, no binding parameters could be calculated. Binding data were analyzed using software (version 1.0; GraphPad). Figure is representative of at least 3 independent experiments.

  • FIGURE 2. 
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    FIGURE 2. 

    IHC and IF analysis indicates PiB staining does not bind to white matter. Microscopy images of 2 serial sections (7 μm) from frontal cortex of AD patient (A) and centrum semiovale from age-matched HC (B) and AD patient (C). First section was immunostained with antibody to Aβ (1E8) to identify Aβ plaques; second serial section was stained with 100 μM PiB. Presence of Aβ plaques was detected in AD frontal cortex sections (black arrowheads) and colocalized with positive PiB staining (white arrowheads). Centrum semiovale sections exhibited no immunoreactivity with 1E8, indicating absence of plaques (B and C). At higher magnification, PiB staining was observed to highlight blood vessels. (D) Serial sections (5 μm) isolated from gray matter (frontal cortex; top) and white matter (centrum semiovale; bottom) of patient with DLB who underwent 11C-PiB PET 23 mo before his death. Sections (from left to right) were stained with antibodies to Aβ (1E8) to Aβ plaques, PiB, α-syn (97/8), and tau-protein (Dako) and stained with PiB (100 μM). Presence of Aβ plaques was detected in DLB frontal cortex sections and colocalized with positive PiB staining. Centrum semiovale sections exhibited no immunoreactivity with any reagent used, indicating absence of Aβ plaques, Lewy bodies, or neurofibrillary tangles. Images were taken on Leica microscope. Scale bars, 50 μm. α-syn = α-synuclein.

  • FIGURE 3. 
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    FIGURE 3. 

    Time–activity curves demonstrate no difference in 11C-PiB clearance rates in white matter of all patients analyzed. Time–activity curves demonstrate uptake and clearance of 11C-PiB in frontal cortex (A) and white matter (B). There is greater retention of PiB in frontal cortex of AD patients and to lesser extent in DLB patients than in HCs. In contrast, there was no significant difference in rate of 11C-PiB clearance in all groups analyzed. SUV = standardized uptake value.

Tables

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    TABLE 1

    ELISA Analysis of Aβ in Human Brain Tissue Homogenates

    TissueAβ1–40 (pmol/g protein)Aβ1–42 (pmol/g protein)Total Aβ (pmol/g protein)
    White matter (centrum semiovale)
     AD (n = 3)2.98 ± 0.1313.37 ± 2.8716.35 ± 3.0
     HC (n = 3)0.77 ± 0.058.12 ± 5.468.89 ± 5.5
    Gray matter (frontal cortex)
     AD (n = 3)128.0 ± 39.01,082.0 ± 337.01,210.0 ± 376.0
     HC (n = 3)4.61 ± 0.134.20 ± 0.618.81 ± 0.74
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    TABLE 2

    Group Mean Demographic Data and PiB DVRs and Clearance Values in Aging HCs and Patients with Dementia

    PiB DVR and clearance value
    Demographic dataHCs (n = 27)AD patients (n = 17)DLB patients (n = 10)
    Age (y)72.6 ± 6.9 (range, 59–84)74.0 ± 11.3 (range, 56–91)72.0 ± 5.4 (range, 63–81)
    Female:male13:149:82:8
    Education (y)12.5 ± 3.512.3 ± 4.89.3 ± 0.9
    MMSE29.2 ± 0.922.1 ± 5.5*20.8 ± 7.2*
    Clinical dementia rating0.0 ± 0.01.2 ± 0.7*1.6 ± 0.8*
    ApoE ε4/non ε48/1910/77/3
    Neocortical† DVR1.22 ± 0.211.99 ± 0.23*1.67 ± 0.32*‡
    White matter DVR1.39 ± 0.19§1.36 ± 0.24§1.33 ± 0.36
    Neocortical clearance t1/2 (min)68.7 ± 11.6112.5 ± 28.3*94.6 ± 25.7*
    White matter clearance t1/2 (min)224.4 ± 89.9§268.7 ± 98.7§229.1 ± 107.0§
    • ↵* Statistically significant results, compared with controls (P < 0.05).

    • ↵† Neocortex comprises average DVR values for frontal, parietal, cingulate, occipital, and lateral temporal cortices.

    • ↵‡ Statistically significant results for DLB patients, compared with AD patients (P < 0.05).

    • ↵§ Statistically significant results for white matter, compared with gray matter (P < 0.05).

    • ApoE = apolipoprotein E.

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Journal of Nuclear Medicine: 50 (2)
Journal of Nuclear Medicine
Vol. 50, Issue 2
February 2009
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Characterization of PiB Binding to White Matter in Alzheimer Disease and Other Dementias
Michelle T. Fodero-Tavoletti, Christopher C. Rowe, Catriona A. McLean, Laura Leone, Qiao-Xin Li, Colin L. Masters, Roberto Cappai, Victor L. Villemagne
Journal of Nuclear Medicine Feb 2009, 50 (2) 198-204; DOI: 10.2967/jnumed.108.057984

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Characterization of PiB Binding to White Matter in Alzheimer Disease and Other Dementias
Michelle T. Fodero-Tavoletti, Christopher C. Rowe, Catriona A. McLean, Laura Leone, Qiao-Xin Li, Colin L. Masters, Roberto Cappai, Victor L. Villemagne
Journal of Nuclear Medicine Feb 2009, 50 (2) 198-204; DOI: 10.2967/jnumed.108.057984
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