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Chunk #51 — Results — Deconvolution of bulk RNA-seq of non-demented and AD brains shows a characteristic signature for neurodegeneration

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Genetic variants associated with Alzheimer's disease confer different cerebral cortex cell-type population structure.
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We also analyzed data from the MSBB, which contains bulk RNA-seq for four additional cerebral cortex areas (APC, STG, PHG, IFG). Replicating our findings from the Mayo dataset, we observed a significant lower relative proportion in neurons and increase in astrocytes in all four areas (Table 2; Fig. 2; and Additional file 1: Table S6). The strongest effect size was detected in the PHG and STG (p < 3.49 × 10−07) (Table 2; Additional file 1: Table S8). Neuropathological studies have described that the PHG is one of the first brain areas in which AD pathology occurs [64–66]. We also observed a significant and strong correlation between neuronal and astrocyte relative proportions and the last ascertained clinical status (CDR), the number of amyloid plaques and Braak staging (Table 2; Fig. 2; Additional file 1: Figure S7).