d64a71ba9ef250c5a607ad7d50c14916  pmc_11702304.pdf
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Title:           Contributions of connectional pathways to shaping Alzheimer’s disease pathologies
Subject:         DOI: 10.1093/braincomms/fcae459; Brain Communications, 7, 1, 2025-01-06.; Abstract: 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 
Keywords:        Alzheimer’s disease; pathology spreading; structural connectivity; functional connectivity; relative importance analysis
Author:          Salma Bougacha
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      Title: Contributions of connectional pathways to shaping Alzheimer’s disease pathologies
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        Title: Introduction
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       Item: 
        Title: Materials and methods
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         Item: 
          Title: Data description
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           Item: 
            Title: Alzheimer’s disease patients and matched controls
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            Title: Middle-aged healthy adults
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              Title: Cam-CAN dataset
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              Title: IMAP dataset
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          Title: Data preprocessing
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            Title: ADNI structural MRI and PET imaging preprocessing
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            Title: Cam-CAN diffusion MRI preprocessing
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            Title: IMAP structural MRI preprocessing
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          Title: Quantification of pathologies
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            Title: Determination of individual patients’ biomarkers patterns
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            Title: Identification of brain maximal pathology sites
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            Title: Determination of group-level regional biomarkers
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          Title: Healthy middle-aged brain characteristics
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            Title: Structural connectome
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            Title: Inter-regional cortical distance network
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          Title: Computation of pathologies predictors and confounding variables
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          Title: Statistical analyses
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            Title: Cross-validated regression and relative importance analyses
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            Title: Bootstrap confidence intervals
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            Title: Comparison of relative contributions between APOE-ɛ4-positive and negative patients
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          Title: Visualizations
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        Title: Results
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          Title: Structural and functional topological descriptors showed partly distinct patterns
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         Item: 
          Title: Structural and functional topological proximity to maximal pathology sites were weakly correlated
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          Title: Connectivity patterns shaped Alzheimer’s disease through concurrent mechanisms
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         Item: 
          Title: APOE-ɛ4 carriage affected contributions consistently across all biomarkers
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        Title: Discussion
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       Item: 
        Title: Supplementary material
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       Item: 
        Title: Acknowledgements
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       Item: 
        Title: Funding
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       Item: 
        Title: Competing interests
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        Title: Data availability
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   Type: CRC32
  Checksum: d64a71ba9ef250c5a607ad7d50c14916
   Type: MD5
  Checksum: b94c67c4212773add4d4236aaf20bd73532feaf5
   Type: SHA-1
  Checksum: d977dbd06a1a9bac817573f969ff5136fde17402acb982327b0584f0711bb67b
   Type: SHA-256