Biology subjects

Sanchez-Rodriguez, L.

Publications and source records attributed to Sanchez-Rodriguez, L..

2 recordsLinked to original sources

bioRxiv2025

Translating the Post-Mortem Brain Multi-Omics Molecular Taxonomy of Alzheimer's Dementia to Living Humans

Alzheimers disease (AD) dementia is characterized by significant molecular and phenotypic heterogeneity, which confounds its mechanistic understanding, diagnosis, and effective treatment. In this study, we harness the most comprehensive dataset of paired ante-mortem blood omics, clinical, psychological, and post-mortem brain multi-omics data and neuroimaging to extensively characterize and translate the molecular taxonomy of AD dementia to living individuals. First, utilizing a comprehensive integration of eight complementary molecular layers from brain multi-omics data (N = 1,189), we identified three distinct molecular AD dementia subtypes exhibiting strong associations with cognitive decline, sex, psychological traits, brain morphology, and characterized by specific cellular and molecular drivers involving immune, vascular, and oligodendrocyte precursor cells. Next, in a significant translational effort, we developed predictive models to convert these advanced brain-derived molecular profiles (AD dementia pseudotimes and subtypes) into blood-, MRI- and psychological traits-based markers. The translation results underscore both the promise of these models and the opportunities for further enhancement. Our findings enhance the understanding of AD heterogeneity, underscore the value of multi-scale molecular approaches for elucidating causal mechanisms, and lay the groundwork for the development of novel therapies in living persons that target multi-level brain molecular subtypes of AD dementia.

neuroscience↗

bioRxiv2019

Estimation of Global and Local Complexities of Brain Networks: A Random Walks Approach

The complexity of brain activity has been observed at many spatial scales and there exists increasing evidence supporting its use in differentiating between mental states and disorders. Here we proposed a new measure of network (global) complexity that is constructed as the sum of the complexities of its nodes (i.e, local complexity). The local complexity of each node is regarded as an index that compares the sample entropy of the time series generated by the movement of a random walker on the network resulting from removing the node and its connections, with the sample entropy of the time series obtained from a regular lattice (the ordered state) and an Erdos-Renyi network (disordered state). We studied the complexity of fMRI-based resting-state functional networks. We found that positively correlated, or \"pos\", network comprising only the positive functional connections has higher complexity than the anticorrelation (\"neg\") network (comprising the negative functional connections) and the network consisting of the absolute value of all connections (\"abs\"). We also found a significant correlation between complexity and the strength of functional connectivity. For the pos network this correlation is significantly weaker at the local scale compared to the global scale, whereas for the neg network the link is stronger at the local scale than at the global scale, but still weaker than for the pos network. Our results suggest that the pos network is related to the information processing in the brain and should be used for functional connectivity analysis instead of the abs network as is usually done.

neuroscience↗