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Chunk #4 — RESULTS — Aberrant mRNA splicing in Alzheimer’s disease

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Integrative transcriptome analyses of the aging brain implicate altered splicing in Alzheimer's disease susceptibility.
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We deeply sequenced RNA from frozen DLFPC samples obtained at autopsy from 450 participants in either the Religious Order Study (ROS) or the Memory and Aging Project (MAP), two prospective cohort studies of aging that include brain donation. All subjects were without known dementia at study entry. During the study, some subjects experienced cognitive decline, and, at autopsy, they displayed a range of amyloid-β and Tau pathology, with 60% of subjects having a pathologic diagnosis of Alzheimer’s disease17,18 (Supplementary Table 1). We have previously reported changes in RNA expression level in relation to Alzheimer’s disease in these data19.