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Publication : Transcriptional Signatures of Tau and Amyloid Neuropathology.

First Author  Castanho I Year  2020
Journal  Cell Rep Volume  30
Issue  6 Pages  2040-2054.e5
PubMed ID  32049030 Mgi Jnum  J:284855
Mgi Id  MGI:6391837 Doi  10.1016/j.celrep.2020.01.063
Citation  Castanho I, et al. (2020) Transcriptional Signatures of Tau and Amyloid Neuropathology. Cell Rep 30(6):2040-2054.e5
abstractText  Alzheimer's disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of beta-amyloid in the neocortex. We use transgenic mice harboring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the progression of tau and amyloid pathology. rTg4510 mice are characterized by widespread transcriptional differences in the entorhinal cortex with changes paralleling neuropathological burden across multiple brain regions. Differentially expressed transcripts overlap with genes identified in genetic studies of familial and sporadic AD. Systems-level analyses identify discrete co-expression networks associated with the progressive accumulation of tau that are enriched for genes and pathways previously implicated in AD pathology and overlap with co-expression networks identified in human AD cortex. Our data provide further evidence for an immune-response component in the accumulation of tau and reveal molecular pathways associated with the progression of AD neuropathology.
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