Abstract
| Original language | English |
|---|---|
| Article number | e12124 |
| Pages (from-to) | e12124 |
| Journal | Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2021 |
Keywords
- Amyloid beta (Aβ)
- Diffusion tensor imaging (DTI)
- Magnetic resonance imaging (MRI)
- Positron emission tomography (PET)
- Preclinical Alzheimer’s disease (AD)
- White matter microstructure
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In: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol. 13, No. 1, e12124, 2021, p. e12124.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - White matter microstructure disruption in early stage amyloid pathology
AU - Collij, Lyduine E.
AU - Ingala, Silvia
AU - Top, Herwin
AU - Wottschel, Viktor
AU - Stickney, Kristine E.
AU - Tomassen, Jori
AU - Konijnenberg, Elles
AU - Kate, Mara Ten
AU - Sudre, Carole
AU - Alves, Isadora Lopes
AU - Yaqub, Maqsood M.
AU - Wink, Alle Meije
AU - van ‘t Ent, Dennis
AU - Scheltens, Philip
AU - van Berckel, Bart N. M.
AU - Visser, Pieter Jelle
AU - Barkhof, Frederik
AU - den Braber, Anouk
N1 - Funding Information: L.E. Collij S. Ingala, H. Top, V. Wottschel, K. Stickney, J. Tomassen, E. Konijnenberg, M. Ten Kate, C. Sudre, I. Lopes Alves, M.M. Yaqub, A.M. Wink, and D. Van ‘t Ent report no disclosures relevant to the manuscript. P. Scheltens received grants from GE Healthcare, Piramal, and Merck, paid to his institution; he has received speaker’s fees paid to the institution Alzheimer Center, VU University Medical Center, Lilly, GE Healthcare, and Roche. B.N.M. van Berckel reports no disclosures relevant to the manuscript. P.J. Visser has served as member of the advisory board of Roche Diagnostics. Dr Visser received nonfinancial support from GE Healthcare, research support from Biogen, and grants from Bristol-Myers Squibb, EU/EFPIA Innovative Medicines Initiative Joint Undertaking, and EU Joint Programme–Neurodegenerative Disease Research (JPND and ZonMw). F. Barkhof received payment and honoraria from Bayer Genzyme, Biogen-Idec, TEVA, Merck, Novartis, Roche, IXICO Ltd, GeNeuro, and Apitope Ltd for consulting; payment from the IXICOLtd, and MedScape for educational presentations; research support via grants from EU/EFPIA Innovative Medicines Initiative Joint Undertaking (AMYPAD consortium), EuroPOND (H2020), UK MS Society, Dutch MS Society, PICTURE (IMDI-NWO), NIHR UCLH Biomedical Research Centre (BRC), and ECTRIMS-MAGNIMS. A. Den Braber reports no disclosures relevant to the manuscript. Funding Information: The authors want to thank all PreclinAD participants for their efforts to join and complete this demanding study and our colleagues of The Netherlands Twin Register for referring participants. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under European Medical Information Framework (EMIF) grant agreement No. 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies in-kind contribution. The project leading to this paper has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) grant agreement No. 115952 and European Prevention of Alzheimer’s Dementia (EPAD) grant No. 115736. This Joint Undertaking receives the support from the European Union’s Horizon 2020 Research and Innovation Programme and EFPIA. Frederik Barkhof is supported by the National Institute for Health Research University College London Hospitals (NIHR UCLH) Biomedical Research Centre. This work also received in-kind sponsoring of the PET-tracer from General Electric (GE) Healthcare. This communication reflects the views of the authors and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein. Funding Information: The authors want to thank all PreclinAD participants for their efforts to join and complete this demanding study and our colleagues of The Netherlands Twin Register for referring participants. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under European Medical Information Framework (EMIF) grant agreement No. 115372, resources of which are composed of financial contribution from the European Union?s Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies in-kind contribution. The project leading to this paper has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Amyloid Imaging to Prevent Alzheimer?s Disease (AMYPAD) grant agreement No. 115952 and European Prevention of Alzheimer?s Dementia (EPAD) grant No. 115736. This Joint Undertaking receives the support from the European Union?s Horizon 2020 Research and Innovation Programme and EFPIA. Frederik Barkhof is supported by the National Institute for Health Research University College London Hospitals (NIHR UCLH) Biomedical Research Centre. This work also received in-kind sponsoring of the PET-tracer from General Electric (GE) Healthcare. This communication reflects the views of the authors and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.Additional supporting information may be found online in the Supporting Information section at the end of the article. Publisher Copyright: © 2021 The Authors. Alzheimer. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - Introduction: Amyloid beta (Aβ) accumulation is the first pathological hallmark of Alzheimer’s disease (AD), and it is associated with altered white matter (WM) microstructure. We aimed to investigate this relationship at a regional level in a cog-nitively unimpaired cohort. Methods: We included 179 individuals from the European Medical Information Framework for AD (EMIF-AD) preclinAD study, who underwent diffusion magnetic resonance (MR) to determine tract-level fractional anisotropy (FA); mean, radial, and axial diffusivity (MD/RD/AxD); and dynamic [18F]flutemetamol) positron emission tomogra-phy (PET) imaging to assess amyloid burden. Results: Regression analyses showed a non-linear relationship between regional amyloid burden and WM microstructure. Low amyloid burden was associated with increased FA and decreased MD/RD/AxD, followed by decreased FA and increased MD/RD/AxD upon higher amyloid burden. The strongest association was observed between amyloid burden in the precuneus and body of the corpus callosum (CC) FA and diffusivity (MD/RD) measures. In addition, amyloid burden in the anterior cingu-late cortex strongly related to AxD and RD measures in the genu CC. Discussion: Early amyloid deposition is associated with changes in WM microstruc-ture. The non-linear relationship might reflect multiple stages of axonal damage.
AB - Introduction: Amyloid beta (Aβ) accumulation is the first pathological hallmark of Alzheimer’s disease (AD), and it is associated with altered white matter (WM) microstructure. We aimed to investigate this relationship at a regional level in a cog-nitively unimpaired cohort. Methods: We included 179 individuals from the European Medical Information Framework for AD (EMIF-AD) preclinAD study, who underwent diffusion magnetic resonance (MR) to determine tract-level fractional anisotropy (FA); mean, radial, and axial diffusivity (MD/RD/AxD); and dynamic [18F]flutemetamol) positron emission tomogra-phy (PET) imaging to assess amyloid burden. Results: Regression analyses showed a non-linear relationship between regional amyloid burden and WM microstructure. Low amyloid burden was associated with increased FA and decreased MD/RD/AxD, followed by decreased FA and increased MD/RD/AxD upon higher amyloid burden. The strongest association was observed between amyloid burden in the precuneus and body of the corpus callosum (CC) FA and diffusivity (MD/RD) measures. In addition, amyloid burden in the anterior cingu-late cortex strongly related to AxD and RD measures in the genu CC. Discussion: Early amyloid deposition is associated with changes in WM microstruc-ture. The non-linear relationship might reflect multiple stages of axonal damage.
KW - Amyloid beta (Aβ)
KW - Diffusion tensor imaging (DTI)
KW - Magnetic resonance imaging (MRI)
KW - Positron emission tomography (PET)
KW - Preclinical Alzheimer’s disease (AD)
KW - White matter microstructure
UR - http://www.scopus.com/inward/record.url?scp=85108240853&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/dad2.12124
DO - https://doi.org/10.1002/dad2.12124
M3 - Article
C2 - 33816751
SN - 2352-8729
VL - 13
SP - e12124
JO - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
JF - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
IS - 1
M1 - e12124
ER -