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August 04, 2020; 95 (5) ArticleOpen Access

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

Laura E. Jonkman, Martijn D. Steenwijk, Nicky Boesen, Annemieke J.M. Rozemuller, View ORCID ProfileFrederik Barkhof, Jeroen J.G. Geurts, Linda Douw, Wilma D.J. van de Berg
First published July 13, 2020, DOI: https://doi.org/10.1212/WNL.0000000000009910
Laura E. Jonkman
From the Departments of Anatomy and Neurosciences (L.E.J., M.D.S., N.B., J.J.G.G., L.D., W.D.J.v.d.B.), Pathology (A.J.M.R.), and Radiology and Nuclear Medicine (F.B.), Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Martijn D. Steenwijk
From the Departments of Anatomy and Neurosciences (L.E.J., M.D.S., N.B., J.J.G.G., L.D., W.D.J.v.d.B.), Pathology (A.J.M.R.), and Radiology and Nuclear Medicine (F.B.), Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Nicky Boesen
From the Departments of Anatomy and Neurosciences (L.E.J., M.D.S., N.B., J.J.G.G., L.D., W.D.J.v.d.B.), Pathology (A.J.M.R.), and Radiology and Nuclear Medicine (F.B.), Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Annemieke J.M. Rozemuller
From the Departments of Anatomy and Neurosciences (L.E.J., M.D.S., N.B., J.J.G.G., L.D., W.D.J.v.d.B.), Pathology (A.J.M.R.), and Radiology and Nuclear Medicine (F.B.), Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Frederik Barkhof
From the Departments of Anatomy and Neurosciences (L.E.J., M.D.S., N.B., J.J.G.G., L.D., W.D.J.v.d.B.), Pathology (A.J.M.R.), and Radiology and Nuclear Medicine (F.B.), Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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  • ORCID record for Frederik Barkhof
Jeroen J.G. Geurts
From the Departments of Anatomy and Neurosciences (L.E.J., M.D.S., N.B., J.J.G.G., L.D., W.D.J.v.d.B.), Pathology (A.J.M.R.), and Radiology and Nuclear Medicine (F.B.), Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Linda Douw
From the Departments of Anatomy and Neurosciences (L.E.J., M.D.S., N.B., J.J.G.G., L.D., W.D.J.v.d.B.), Pathology (A.J.M.R.), and Radiology and Nuclear Medicine (F.B.), Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Wilma D.J. van de Berg
From the Departments of Anatomy and Neurosciences (L.E.J., M.D.S., N.B., J.J.G.G., L.D., W.D.J.v.d.B.), Pathology (A.J.M.R.), and Radiology and Nuclear Medicine (F.B.), Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.
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Relationship between β-amyloid and structural network topology in decedents without dementia
Laura E. Jonkman, Martijn D. Steenwijk, Nicky Boesen, Annemieke J.M. Rozemuller, Frederik Barkhof, Jeroen J.G. Geurts, Linda Douw, Wilma D.J. van de Berg
Neurology Aug 2020, 95 (5) e532-e544; DOI: 10.1212/WNL.0000000000009910

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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.

Glossary

Aβ42=
β-amyloid 42;
AD=
Alzheimer disease;
CI=
confidence interval;
DAB=
diaminobenzidine tetrahydrochloride dehydrate;
DTI=
diffusion tensor imaging;
FDR=
false discovery rate;
FLAIR=
fluid-attenuated inversion recovery;
GM=
gray matter;
NABCA=
Normal Aging Brain Collection Amsterdam;
NFT=
neurofibrillary tangle;
NIA-AA=
National Institute of Aging–Alzheimer's Association;
p-tau=
hyperphosphorylated tau;
TBS=
Tris-buffered saline;
TE=
echo time;
TI=
inversion time;
TR=
repetition time;
WM=
white matter

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • The Article Processing Charge was funded by Alzheimer Association (Research Fellowship AARF-18-566459).

  • Received June 1, 2019.
  • Accepted in final form January 14, 2020.
  • Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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.

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