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Aguillon, D.

Publications and source records attributed to Aguillon, D..

2 recordsLinked to original sources

Reproducible Neuronal Components found using Group Independent Component Analysis in Resting State Electroencephalographic Data

ObjectiveEvaluate the reliability of neural components obtained from the appli-cation of the group ICA (gICA) methodology to resting-state EEG datasets acquired from multiple sites. MethodsFive databases from three sites, covering a total of 292 healthy subjects, were analyzed. Each dataset was segmented into groups of 15 subjects, for a total of 19 groups. Data were pre-processed using an automatic pipeline leveraging robust average referencing, wavelet-ICA and automatic rejection of epochs. On each group, stable gICA decompositions were calculated using the ICASSO methodology through a range of orders of decompositions. Each order was characterized by reliability and neuralness metrics, which were evaluated to select a single order of decomposition. Finally, using the decompositions of the selected order, a clustering analysis was performed to find the common components across the 19 groups. Each cluster was characterized by the mean scalp map, its dipole generator with its localization in Talairach coordinates, the spectral behavior of the associated time-series of the components, the assigned ICLabel class and metrics that reflected their reproducibility. ResultsLower order of decompositions benefits the gICA methodology. At this, using an order of ten, the number of reproducible components with high neuronal information tends to be around nine. Of these, the bilateral motor, frontal medial, and occipital neuronal components were the most reproducible across the different datasets, appearing in more than 89% of the 19 groups evaluated. ConclusionWe developed a workflow that allows finding reproducible spatial filters between different data sets. This contributes to the improvement of the spatial resolution of the EEG as a brain mapping technique.

neuroscience↗

APOE3 Christchurch modulates tau phosphorylation and regulates β-catenin/Wnt/Cadherin signaling in induced pluripotent stem cell-derived cerebral organoids from Alzheimer's cases

Alzheimers disease (AD) is the most common cause of dementia among older adults. APOE3 Christchurch (R136S, APOE3Ch) variant homozygosity was reported in an individual with extreme resistance to autosomal dominant AD due to the PSEN1 E280A mutation. This subject had a delayed clinical age at onset and resistance to tauopathy and neurodegeneration despite extremely high amyloid plaque burden. We established induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and from a non-protected kindred control (with PSEN1 E280A and APOE3/3). We used CRISPR/Cas9 gene editing to successfully remove the APOE3Ch to wild type in iPS cells from the protected case and to introduce the APOE3Ch as homozygote in iPS cells from the non-protected case to examine causality. We found significant reduction of tau phosphorylation (pTau 202/205 and pTau396) in cerebral organoids with the APOE3Ch variant, consistent with the strikingly reduced tau pathology found in the resistant case. We identified Cadherin and Wnt pathways as signaling mechanisms regulated by the APOE3Ch variant through single cell RNA sequencing in cerebral organoids. We also identified elevated {beta}-catenin protein, a regulator of tau phosphorylation, as a candidate mediator of APOE3Ch resistance to tauopathy. Our findings show that APOE3Ch is necessary and sufficient to confer resistance to tauopathy in an experimental ex-vivo model establishing a foundation for the development of novel, protected case-inspired therapeutics for tauopathies, including Alzheimers.

neuroscience↗