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Sakmar, The Rockefeller Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA245791Homo sapiensAlternative polyadenylation (APA) contributes to post-transcriptional regulation, but its role in Alzheimer’s disease (AD) is largely unknown. Using high-resolution SQUARE multiple 3’ primer-based sequencing, we discovered massive APA differences in temporal gyrus tissues from demented AD patients compared to either healthy controls or non-demented donors with AD neuropathology (NDWP). Advanced statistics, microfluidics RT-PCR and protein measurements validated known and novel APA-modified 3’-intact transcripts. Moreover, APA modifications, more than total transcript counts, distinguished AD patients from both controls and NDWP donors and identified cell type-characteristic, cognition-associated and neuropathology-related changes. AD-enhanced APA variants included known therapeutic targets of brain, vascular and autoimmune disorders, predicting co-involvement of these target genes in AD progression AD/NDWP increases in 3’-intact proteinopathy-related hnRNP mRNAs were inversely associated with protein decreases, whereas NDWP-potentiated cognition was accompanied by distinct ATP and mitochondrial variants. APA variations thus provide a novel resource of unique value for both basic and translational neuroscience researchers. Overall design: Examination of poly adenylation sites in brain tissues of Alzheimer's disease patients, non-demented with Alzheimer's disease like pathology and non-demented without Alzheimer's disease like pathology.xref:PubMed:28630030ENAfalseHomo sapiensAlternative poly(A) in Alzheimer's disase2025-09-242023-03-28PRJNA245791GSE57152960628630030