Transcriptional Signatures of Tau and Amyloid Neuropathology.

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 Rep

journal_title

Cell reports

authors

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 J

doi

10.1016/j.celrep.2020.01.063

subject

Has Abstract

pub_date

2020-02-11 00:00:00

pages

2040-2054.e5

issue

6

issn

2211-1247

pii

S2211-1247(20)30088-7

journal_volume

30

pub_type

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