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Contributions of connectional pathways to shaping Alzheimer's disease pathologies
Bougacha, Salma (Normandie University)
Roquet, Daniel (Normandie University)
Landeau, Brigitte (Normandie University)
Saul, Elise (Normandie University)
Naveau, Mikaël (Normandie University)
Sherif, Siya (Normandie University)
Bejanin, Alexandre (Normandie University)
Dhenain, Marc (Université Paris-Saclay)
Raj, Ashish (University of California)
Vivien, Denis (Normandie University)
Chetelat, Gaël (Normandie University)

Data: 2025
Resum: Four important imaging biomarkers of Alzheimer's disease, namely grey matter atrophy, glucose hypometabolism and amyloid-β and tau deposition, follow stereotypical spatial distributions shaped by the brain network of structural and functional connections. In this case-control study, we combined several predictors reflecting various possible mechanisms of spreading through structural and functional pathways to predict the topography of the four biomarkers in amyloid-positive patients while controlling for the effect of spatial distance along the cortex. For each biomarker, we quantified the relative contribution of each predictor to the variance explained by the model. We also compared the contribution between apolipoprotein E-ɛ4 carriers and non-carriers. We found that topological proximity to areas of maximal pathology through the functional connectome explained significant parts of variance for all biomarkers and that functional pathways totalized more than 30% of contributions for hypometabolism and amyloid load. By contrast, atrophy and tau load were mainly predicted by structural pathways, with major contributions from inter-regional diffusion. The ɛ4 allele modulated contributions to the four biomarkers in a way consistent with compromised brain connectomics in carriers. Our approach can be used to assess the contribution of concurrent mechanisms in other neurodegenerative diseases and the possible modifying impact of relevant factors on this contribution. The relative importance of different connectional pathways in shaping Alzheimer's disease pathologies is unknown. Bougacha et al. reported that functional and structural connectome differently contribute to the spreading of grey matter atrophy, glucose hypometabolism and amyloid-β and tau deposition spread in apolipoprotein E-ɛ4 carrier and non-carrier patients with Alzheimer's disease.
Ajuts: European Commission 667696
Instituto de Salud Carlos III 20/00038
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Alzheimer's disease ; Pathology spreading ; Structural connectivity ; Functional connectivity ; Relative importance analysis
Publicat a: Brain Communications, Vol. 7 (january 2025) , ISSN 2632-1297

DOI: 10.1093/braincomms/fcae459
PMID: 39763634


16 p, 1.4 MB

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