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. 2020:27:102333.
doi: 10.1016/j.nicl.2020.102333. Epub 2020 Jul 2.

The combined effect of amyloid-β and tau biomarkers on brain atrophy in dementia with Lewy bodies

Carla Abdelnour  1 , Daniel Ferreira  2 , Ketil Oppedal  3 , Lena Cavallin  4 , Olivier Bousiges  5 , Lars Olof Wahlund  2 , Jakub Hort  6 , Zuzana Nedelska  6 , Alessandro Padovani  7 , Andrea Pilotto  7 , Laura Bonanni  8 , Milica G Kramberger  9 , Mercè Boada  10 , Eric Westman  11 , Javier Pagonabarraga  12 , Jaime Kulisevsky  12 , Frédéric Blanc  13 , Dag Aarsland  14
Affiliations

The combined effect of amyloid-β and tau biomarkers on brain atrophy in dementia with Lewy bodies

Carla Abdelnour et al. Neuroimage Clin. 2020.

Abstract

Background: Alzheimer's disease (AD)-related pathology is frequently found in patients with dementia with Lewy bodies (DLB). However, it is unknown how amyloid-β and tau-related pathologies influence neurodegeneration in DLB. Understanding the mechanisms underlying brain atrophy in DLB can improve our knowledge about disease progression, differential diagnosis, drug development and testing of anti-amyloid and anti-tau therapies in DLB.

Objectives: We aimed at investigating the combined effect of CSF amyloid-β42, phosphorylated tau and total tau on regional brain atrophy in DLB in the European DLB (E-DLB) cohort.

Methods: 86 probable DLB patients from the E-DLB cohort with CSF and MRI data were included. Random forest was used to analyze the association of CSF biomarkers (predictors) with visual rating scales for medial temporal lobe atrophy (MTA), posterior atrophy (PA) and global cortical atrophy scale-frontal subscale (GCA-F) (outcomes), including age, sex, education and disease duration as extra predictors.

Results: DLB patients with abnormal MTA scores had abnormal CSF Aβ42, shorter disease duration and older age. DLB patients with abnormal PA scores had abnormal levels of CSF Aβ42 and p-tau, older age, lower education and shorter disease duration. Abnormal GCA-F scores were associated with lower education, male sex, and older age, but not with any AD-related CSF biomarker.

Conclusions: This study shows preliminary data on the potential combined effect of amyloid-β and tau-related pathologies on the integrity of posterior brain cortices in DLB patients, whereas only amyloid-β seems to be related to MTA. Future availability of α-synuclein biomarkers will help us to understand the effect of α-synuclein and AD-related pathologies on brain integrity in DLB.

Keywords: Alzheimer disease; Atrophy; Biomarkers; Lewy body disease; Neuroimaging.

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Conflict of interest statement

  1. 1.

    Carla Abdelnour: Carla Abdelnour has received honoraria from Zambon and Schwabe.

  2. 2.

    Daniel Ferreira: none.

  3. 3.

    Ketil Oppedal: none.

  4. 4.

    Lena Cavallin: none.

  5. 5.

    Frédéric Blanc: none.

  6. 6.

    Oliver Bousiges: none.

  7. 7.

    Lars Olof Wahlund: none.

  8. 8.

    Jakub Hort: none.

  9. 9.

    Zuzana Nedelska: Dr. Nedelska has been supported by IBRO-ISN fellowship 2018.

  10. 10.

    Alessandro Padovani: none.

  11. 11.

    Andrea Pilotto: none.

  12. 12.

    Laura Bonanni: none.

  13. 13.

    Milica Kramberger: none.

  14. 14.

    Mercè Boada: none.

  15. 15.

    Eric Westman: none.

  16. 16.

    Javier Pagonabarraga: none.

  17. 17.

    Jaime Kulisevsky: none.

  18. 18.

    Dag Aarsland: Dr Aarsland has received research support and/or honoraria from Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals and GE Health, and served as paid consultant for H. Lundbeck, Eisai, Heptares, Mentis Cura. Dag Aarsland is a Royal Society Wolfson Research Merit Award Holder and would like to thank the Wolfson Foundation and the Royal Society for their support.

Figures

Fig. 1
Fig. 1
Normal and pathological CSF values of Aβ42 and p-Tau combined with visual rating scales. CSF levels of Aβ42 and p-Tau were dichotomized according the cut-offs of each center into normal or pathological values. MTA, PA and GCA-F visual rating scales were used to measure regional atrophy based on T1-weigthed images. A+= pathological CSF Aβ42; A− = normal CSF Aβ42; T+= pathological CSF p-Tau; T− = normal CSF p-Tau; MTA = medial temporal atrophy scale; PA = posterior atrophy scale; GCA-F = global cortical atrophy scale – frontal subscale; A = anterior part of the brain; P = posterior part of the brain; R = right; L = left.
Fig. 2
Fig. 2
Correlation matrix between visual ratings, CSF biomarkers, and predictors in the random forest models. Asterisk symbols (*) denote p-values < 0.05. MTA = medial temporal atrophy scale; PA = posterior atrophy scale; GCA-F = global cortical atrophy scale – frontal subscale.
See this image and copyright information in PMC

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