Abstract：
:Alzheimer's disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of β-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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Castanho I,Murray TK,Hannon E,Jeffries A,Walker E,Laing E,Baulf H,Harvey J,Bradshaw L,Randall A,Moore K,O'Neill P,Lunnon K,Collier DA,Ahmed Z,O'Neill MJ,Mill Jdoi
10.1016/j.celrep.2020.01.063subject
Has Abstractpub_date
2020-02-11 00:00:00pages
2040-2054.e5issue
6issn
2211-1247pii
S2211-1247(20)30088-7journal_volume
30pub_type
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