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Relationship between β-amyloid and structural network topology in decedents without dementia

Jonkman, LE; Steenwijk, MD; Boesen, N; Rozemuller, AJM; Barkhof, F; Geurts, JJG; Douw, L; (2020) Relationship between β-amyloid and structural network topology in decedents without dementia. Neurology 10.1212/wnl.0000000000009910. (In press). Green open access

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Abstract

Objective To investigate the association between β-amyloid (Aβ) load and postmortem structural network topology in decedents without dementia. Methods Fourteen decedents (mean age at death 72.6 ± 7.2 years) without known clinical diagnosis of neurodegenerative disease and meeting pathology criteria only for no or low Alzheimer disease (AD) pathologic change were selected from the Normal Aging Brain Collection Amsterdam database. In situ brain MRI included 3D T1-weighted images for anatomical registration and diffusion tensor imaging for probabilistic tractography with subsequent structural network construction. Network topologic measures of centrality (degree), integration (global efficiency), and segregation (clustering and local efficiency) were calculated. Tissue sections from 12 cortical regions were sampled and immunostained for Aβ and hyperphosphorylated tau (p-tau), and histopathologic burden was determined. Linear mixed effect models were used to assess the relationship between Aβ and p-tau load and network topologic measures. Results Aβ was present in 79% of cases and predominantly consisted of diffuse plaques; p-tau was sparsely present. Linear mixed effect models showed independent negative associations between Aβ load and global efficiency (β = −0.83 × 10−3, p = 0.014), degree (β = −0.47, p = 0.034), and clustering (β = −0.55 × 10−2, p = 0.043). A positive association was present between Aβ load and local efficiency (β = 3.16 × 10−3, p = 0.035). Regionally, these results were significant in the posterior cingulate cortex (PCC) for degree (β = −2.22, p < 0.001) and local efficiency (β = 1.01 × 10−2, p = 0.014) and precuneus for clustering (β = −0.91 × 10−2, p = 0.017). There was no relationship between p-tau and network topology. Conclusion This study in deceased adults with AD-related pathologic change provides evidence for a relationship among early Aβ accumulation, predominantly of the diffuse type, and structural network topology, specifically of the PCC and precuneus.

Type: Article
Title: Relationship between β-amyloid and structural network topology in decedents without dementia
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/wnl.0000000000009910
Publisher version: https://doi.org/10.1212/WNL.0000000000009910
Language: English
Additional information: This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
URI: https://discovery.ucl.ac.uk/id/eprint/10106014
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