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One of the crucial reasons is also having addressed molecular targets and key neuropathological changes acting too late in the disease, such as A plaques and hyperphosphorylated tau protein deposits (Gody et al., 2016)

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On the host side, transcriptional profiling showed high activity of pattern recognition receptors and expanded gene families involved in innate immunity and lysosomal enzymes

Moreover, the advent of single-cell RNA sequencing technology has enabled researchers to investigate gene expression heterogeneity at the single-cell level, providing a novel perspective on cellular differences and their roles in disease [264, 270]