Insight on AV-45 binding in white and grey matter from histogram analysis: a study on early Alzheimer’s disease patients and healthy subjects

  • Federico Nemmi
  • Laure Saint-Aubert
  • Djilali Adel
  • Anne-Sophie Salabert
  • Jérémie Pariente
  • Emmanuel J. Barbeau
  • Pierre Payoux
  • Patrice Péran
Original Article



AV-45 amyloid biomarker is known to show uptake in white matter in patients with Alzheimer’s disease (AD), but also in the healthy population. This binding, thought to be of a non-specific lipophilic nature, has not yet been investigated. The aim of this study was to determine the differential pattern of AV-45 binding in white matter in healthy and pathological populations.


We recruited 24 patients presenting with AD at an early stage and 17 matched, healthy subjects. We used an optimized positron emission tomography-magnetic resonance imaging (PET-MRI) registration method and an approach based on an intensity histogram using several indices. We compared the results of the intensity histogram analyses with a more canonical approach based on target-to-cerebellum Standard Uptake Value (SUVr) in white and grey matter using MANOVA and discriminant analyses. A cluster analysis on white and grey matter histograms was also performed.


White matter histogram analysis revealed significant differences between AD and healthy subjects, which were not revealed by SUVr analysis. However, white matter histograms were not decisive to discriminate groups, and indices based on grey matter only showed better discriminative power than SUVr. The cluster analysis divided our sample into two clusters, showing different uptakes in grey, but also in white matter.


These results demonstrate that AV-45 binding in white matter conveys subtle information not detectable using the SUVr approach. Although it is not more efficient than standard SUVr in discriminating AD patients from healthy subjects, this information could reveal white matter modifications.


AV-45 Amyloid Intensity histogram Discrimination analysis Alzheimer’s disease 



This study was supported by a grant from the University Hospital of Toulouse, local grant 2007, and a grant from the Agence Nationale de la Recherche. The authors thank the promoter of this study and Toulouse University Hospital.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

259_2014_2728_MOESM1_ESM.pdf (359 kb)
Supplementary Figure 1 Intensity histograms of grey and white matter of an AD patient (a) and of a healthy control (b). Histograms were derived from grey and white matter probability images thresholded at 0.25, 0.50, 0.75 and 0.95, corresponding respectively to probabilities of 25 %, 50 %, 75 % and 95 % of a voxel of being in grey/white matter. No differences related to the chosen threshold are present. (PDF 358 kb)
259_2014_2728_MOESM2_ESM.pdf (393 kb)
Supplementary Figure 2 White matter mean histograms of AD (red filled squares) and HC (blue filled squares) and white matter histograms of the three AD patients and of the seven HC subjects misclassified in the discriminant analysis performed using white matter indices. The mean histograms were calculated without the misclassified subjects in each group. Vertical dashed-dotted lines in panels a and b mark 25th and 75th percentiles of histograms. (PDF 392 kb)
259_2014_2728_MOESM3_ESM.docx (16 kb)
Supplementary Table 1 (DOCX 15 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Federico Nemmi
    • 1
    • 2
  • Laure Saint-Aubert
    • 1
    • 2
  • Djilali Adel
    • 1
    • 2
    • 3
  • Anne-Sophie Salabert
    • 1
    • 2
    • 3
  • Jérémie Pariente
    • 1
    • 2
    • 4
  • Emmanuel J. Barbeau
    • 4
    • 5
  • Pierre Payoux
    • 1
    • 2
    • 3
  • Patrice Péran
    • 1
    • 2
  1. 1.Inserm, imagerie cérébrale et handicaps neurologiques UMR 825, Centre Hospitalier Universitaire de ToulouseToulouse cedex 9France
  2. 2.Université de Toulouse, UPS, imagerie cérébrale et handicaps neurologiques UMR 825, Centre Hospitalier Universitaire de ToulouseToulouseFrance
  3. 3.Service de Médecine Nucléaire, Pôle ImagerieCentre Hospitalier Universitaire de ToulouseToulouseFrance
  4. 4.Service de neurologie, pôle neurosciencesCentre Hospitalier Universitaire de ToulouseToulouseFrance
  5. 5.Université de Toulouse, UPS, centre de recherche cerveau et cognition, CNRS, CerCoToulouseFrance

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