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Fig. 3 | Alzheimer's Research & Therapy

Fig. 3

From: A novel human tau knock-in mouse model reveals interaction of Abeta and human tau under progressing cerebral amyloidosis in 5xFAD mice

Fig. 3

Correlation of gene expression data of studied mouse models with human data on post mortem brain regions reveals a seemingly protective effect of human tau on amyloid background in 5xFADxhtau-KI mice. Correlation analysis between mouse and human data was performed for 30 AMP-AD co-expression modules from seven brain regions and three clinical cohorts. Mouse effects for the 5xFAD and htau-KI models are relative to age-matched B6 female mice, which were correlated with the effects of human cases versus controls. In addition, an interaction term was introduced to correlate 5xFAD and htau-KI models with the effects of human cases compared to controls. Significant correlations (FDR-adjusted P<0.05) across species are highlighted by black rectangles. A strong positive correlation with immune related co-expression modules in consensus cluster B was observed for 5xFAD mice at 7 and 13 months. A strong negative correlation in modules enriched for genes in mitochondrial function (consensus cluster E) was shown for the htau-KI model solely on the 5xFAD background at the age of 7 months supporting an amyloid-dependent protective effect of htau. This includes modules enriched for specific disease pathways, such as the KEGG oxidative phosphorylation pathway in the PHGblue module from the MSSM cohort. At 13 months, this effect in the 5xFADxhtau-KI model was observed in human co-expression modules linked to extracellular matrix organization and immune function (consensus clusters A and B)

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