PT  - JOURNAL ARTICLE
AU  - Wei-Ting Chen
AU  - Ashley Lu
AU  - Katleen Craessaerts
AU  - Benjamin Pavie
AU  - Carlo Sala Frigerio
AU  - Renzo Mancuso
AU  - Xiaoyan Qian
AU  - Jana Lalakova
AU  - Malte Kühnemund
AU  - Iryna Voytyuk
AU  - Leen Wolfs
AU  - An Snellinx
AU  - Sebastian Munck
AU  - Aleksandra Jurek
AU  - Jose Fernandez Navarro
AU  - Takaomi C Saido
AU  - Joakim Lundeberg
AU  - Mark Fiers
AU  - Bart De Strooper
TI  - Spatial and temporal transcriptomics reveal microglia-astroglia crosstalk in the amyloid-β plaque cell niche of Alzheimer’s disease
AID  - 10.1101/719930
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 719930
4099  - http://biorxiv.org/content/early/2019/08/12/719930.short
4100  - http://biorxiv.org/content/early/2019/08/12/719930.full
AB  - The linear cause-consequence relationship linking amyloid-β peptide (Aβ) accumulation to neuronal dysfunction in Alzheimer disease (AD) is gradually replaced by the concept that Aβ initiates complex inflammatory-like cellular alterations that progressively become Aβ independent and lead to brain dyshomeostasis. Little is known about the pathophysiology of this cellular phase of AD. We use here two orthogonal technologies, Spatial Transcriptomics and in situ sequencing, to analyse the transcriptome changes in cells in the amyloid-β plaque niche in a knock-in mouse model for AD. We identify a multicellular co-expressed gene network of 57 Plaque-Induced Genes (PIGs) that define a series of co-ordinated and spatially restricted microglia, astroglia and oligodendrocyte responses to progressing amyloid plaques encompassing complement, oxidative stress and inflammation. A separate oligodendrocyte network suggests abnormal myelination. Spatial Transcriptomics provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.