Epicentral Disruption of Structural Connectivity in Alzheimer's Disease

Mallio, Carlo Augusto; Schmidt, Ruben; Reus, Marcel A. de; Vernieri, Fabrizio; Quintiliani, Livia; Curcio, Giuseppe; Zobel, Bruno Beomonte; Quattrocchi, Carlo Cosimo; Heuvel, Martijn P. van den

doi:10.1111/cns.12397

Cited by 31 publications

(29 citation statements)

References 61 publications

(89 reference statements)

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“…Results show that AD alters the global and local properties of the scalp-level brain network. The decreased functional synchronization obtained in AD patients compared to healthy controls agrees with previous finding [8], [21]- [23]. Similarly, the decreased global efficiency of the AD network is consistent with [7], [9].…”

Section: Discussionsupporting

confidence: 90%

A scalp-EEG network-based analysis of Alzheimer's disease patients at rest

Kabbara

Falou

Khalil

et al. 2017

2017 Fourth International Conference on Advances in Biomedical Engineering (ICABME)

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Abstract-Most brain disorders including Alzheimer's disease (AD) are related to alterations in the normal brain network organization and function. Exploring these network alterations using non-invasive and easy to use technique is a topic of great interest. In this paper, we collected EEG resting-state data from AD patients and healthy control subjects. Functional connectivity between scalp EEG signals was quantified using the phase locking value (PLV) for 6 frequency bands, θ (4-8 Hz), α1(8-10 Hz), α2(10-13 Hz), ß(13-30 Hz), γ(30-45 Hz), and broad band (0.2-45 Hz). To assess the differences in network properties, graph-theoretical analysis was performed. AD patients showed decrease of mean connectivity, average clustering and global efficiency in the lower alpha band. Positive correlation between the cognitive score and the extracted graph measures was obtained, suggesting that EEG could be a promising technique to derive new biomarkers of AD diagnosis.

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Section: Discussionsupporting

confidence: 90%

A scalp-EEG network-based analysis of Alzheimer's disease patients at rest

Kabbara

Falou

Khalil

et al. 2017

2017 Fourth International Conference on Advances in Biomedical Engineering (ICABME)

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“…The EC and hippocampus are two key vulnerable brain regions in AD, becoming affected in the early stages of AD (Mak et al, 2017, Hett et al, 2019. Disrupted structural connectivity in the EC is also a feature of AD (Mallio et al, 2015). Consistent with the human findings, we also showed structural connectivity deficits in the EC and hippocampal subfields, namely the subiculum.…”

Section: Discussionsupporting

confidence: 89%

Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis

Al-Amin

Grandjean

Klohs

et al. 2020

Preprint

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Although amyloid beta (Aβ) deposition is one of the major causes of white matter (WM) alterations in Alzheimer's disease (AD), little is known about the underlying basis of WM damage and its association with global structural connectivity and network topology. We aimed to dissect the contributions of WM microstructure to structural connectivity and network properties in the ArcAβ mice model of Aβ amyloidosis.We acquired diffusion-weighted images (DWI) of wild type (WT) and ArcAβ transgenic (TG) mice using a 9.4 T MRI scanner. Fixel-based analysis (FBA) was performed to measure fiber tract-specific properties. We also performed three complementary experiments; to identify the global differences in structural connectivity, to compute network properties and to measure cellular basis of white matter alterations.Transgenic mice displayed disrupted structural connectivity centered to the entorhinal cortex (EC) and a lower fiber density and fiber bundle cross-section. In addition, there was a reduced network efficiency and degree centrality in weighted structural connectivity in the transgenic mice. To further examine the underlying neuronal basis of connectivity and network deficits, we performed histology experiments. We found no alteration in myelination and an increased level of neurofilament light (NFL) in the brain regions with disrupted connectivity in the TG mice. Furthermore, TG mice had a reduced number of perineuronal nets (PNN) in the EC.The observed FDC reductions may indicate a decrease in axonal diameter or axon count which would explain the basis of connectivity deficits and reduced network efficiency in TG mice. The increase in NFL suggests a breakdown of axonal integrity, which would reduce WM fiber health.Considering the pivotal role of the EC in AD, Aβ deposition may primarily increase NFL release, damaging PNN in the entorhinal pathway, resulting in disrupted structural connectivity.

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“…The progress of neuroimaging techniques, in particular diffusion magnetic resonance imaging (dMRI) and functional MRI, as well as post-processing (tractography) and network analysis methods, has enabled the in vivo study of the structural and functional connectivity that form the brain connectome. Connectomics has so far confirmed the impairment of network connectivity in AD observed by neuroanatomical and neuropathological studies, supporting the role of white matter degeneration in the disease, and the fact that part of the symptoms are due to disconnection of distant cortical regions (Daianu et al, 2013b(Daianu et al, , 2013aFischer et al, 2015;Mallio et al, 2015;Nir et al, 2012Nir et al, , 2015Prescott et al, 2014).…”

Section: Introductionmentioning

confidence: 73%

“…Numerous studies have focused on subjects with mild cognitive impairment (MCI) who present objective cognitive deficits but are not yet demented (Petersen, 2011;Petersen et al, 2009). Recently, several studies have studied the structural connectome based on diffusion MRI in subjects with MCI and have demonstrated impaired connectivity, similar to that observed in AD with a lower degree of severity (Daianu et al, 2013b(Daianu et al, , 2013aMallio et al, 2015;Prescott et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment

Jacquemont

Fallani

Bertrand

et al. 2017

Neurobiology of Aging

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Using diffusion MRI, we showed that both MCI A-N+ and MCI A+N+ subjects displayed an alteration of the white matter in the fornix and a significant bi-hemispheric network of decreased connections. These network alterations in MCI A+N+ are stronger and more focal than those of MCI A-N+. Only MCI A+N+ subjects exhibited specific changes in hippocampal connectivity and an AD-like alteration pattern. Our results indicate that the connectome disintegration pattern of MCI subgroups differ with respect to brain amyloid and neurodegeneration. Each of these two AD biomarkers induces a connectome alteration that is maximal when they co-exist.

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Epicentral Disruption of Structural Connectivity in Alzheimer's Disease

Abstract: Our results favor an epicentral disruption of structural connectivity in aMCI and AD around entorhinal and hippocampal regions, consistent with the transneuronal spread hypothesis.

Cited by 31 publications

References 61 publications

A scalp-EEG network-based analysis of Alzheimer's disease patients at rest

A scalp-EEG network-based analysis of Alzheimer's disease patients at rest

Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis

Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment

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