Abstract
Multiple neuropathological changes are involved in Alzheimer’s disease (AD). The current study investigated the concurrence of neurodegeneration, increased iron content, atrophy, and demyelination in AD.
Quantitative multiparameter MRI maps providing neuroimaging biomarkers for myelination and iron content along with synaptic density measurements using [18F] UCB-H PET were acquired in 24 AD and 19 Healthy controls (19 males).
The whole brain voxel-wise group comparison revealed demyelination in the right hippocampus, while no significant iron content difference was detected. Bilateral atrophy and synaptic density loss was observed in the hippocampus and amygdala. The multivariate GLM (mGLM) analysis shows a bilateral difference in the hippocampus and amygdala, right pallidum, left fusiform and temporal lobe suggesting that these regions are the most affected despite the diverse changes in brain tissue properties in AD. Demyelination was identified as the most affecting factor in the observed differences.
Here, the mGLM is introduced as an alternative for multiple comparisons between different modalities, reducing the risk of false positives while informing about the co-occurrence of neuropathological processes in AD.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
Funding: This work was supported by the ULiege Research Concerted Action (SLEEPDEM, grant 17/2109) and Walloon Region in the framework of the PIT program PROTHER-WAL under grant agreement No. 7289. [18F]flutemetamol was provided by GE Healthcare. CB is a Senior Research Associate at the F.R.S.-FNRS and CP is a Research Director at the F.R.S.-FNRS.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
All procedures performed in studies involving human participants were approved by the Ethics Committee of the Liege University Hospital (Belgium), reference number EudraCT 2014-000286-50, and were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.”
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Footnotes
New correlation analyses are added to improve the discussion of the results. VBM analysis are added to both univariate and multivariate analyses, to consider the the effect of GM volume alteration.
Data Availability
All data produced in the present study are available upon reasonable request to the authors