2022
DOI: 10.1017/s1431927622005840
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High-Resolution Ex Vivo Tissue Clearing, Lightsheet Imaging, and Data Analysis to Support Macromolecular Drug and Biomarker Distribution in Whole Organs and Tumors

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“…Future model iterations may explore mechanisms such as increased heterogeneity of microglia, subregional variation in the role of Aβ deposition, different sizes of Aβ oligomers and fibrils, and microglial interactions with tau and plaque compaction or using imaging data to initialize simulations. 40,41 This model can also be applied to fractionally up-and downregulate microglial behaviors and can thus be used for exposure-response predictions to yield unique insights into potential pharmacologic interventions that directly modulate microglia activation states and the recently approved plaque clearing immunotherapies such as lecanemab. 42 Furthermore, the addition of other cell types, informed by either AD-specific or generalized data sets, could further expand our understanding of these processes in the larger context of the brain through diverse data integration.…”
Section: Discussionmentioning
confidence: 99%
“…Future model iterations may explore mechanisms such as increased heterogeneity of microglia, subregional variation in the role of Aβ deposition, different sizes of Aβ oligomers and fibrils, and microglial interactions with tau and plaque compaction or using imaging data to initialize simulations. 40,41 This model can also be applied to fractionally up-and downregulate microglial behaviors and can thus be used for exposure-response predictions to yield unique insights into potential pharmacologic interventions that directly modulate microglia activation states and the recently approved plaque clearing immunotherapies such as lecanemab. 42 Furthermore, the addition of other cell types, informed by either AD-specific or generalized data sets, could further expand our understanding of these processes in the larger context of the brain through diverse data integration.…”
Section: Discussionmentioning
confidence: 99%