p(MGI:Cdkn2a)
In 15-month-old mice with heavy Abeta deposition and phosphorylated tau, but lacking NFT pathology (Orr et al., 2014), Cdkn2a expression was not elevated (Figure 4e). These data indicate that Cdkn2a expression was neither a response to general protein accumulation, nor to pre-NFT tau pathology, but instead required the presence of NFTs PubMed:30126037
Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice PubMed:30126037
Consistent with NFTs from human AD, mouse NFTs also caused significant activation scores for IFNG, TNF, IL-1B, as well as enrichment in other senescence associated JAK, STAT, CDKN2A and BCL2 predicted upstream regulators (Figure 1c) indicating translational relevance for using tauNFT mice to explore our hypothesis PubMed:30126037
Cdkn2a gene expression increased significantly during this age interval, and at 28 months of age tauWT Cdkn2a expression was similar to that of 16-month-old tauNFT mice (Figure 4c) PubMed:30126037
In 15-month-old mice with heavy Abeta deposition and phosphorylated tau, but lacking NFT pathology (Orr et al., 2014), Cdkn2a expression was not elevated (Figure 4e). These data indicate that Cdkn2a expression was neither a response to general protein accumulation, nor to pre-NFT tau pathology, but instead required the presence of NFTs PubMed:30126037
Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice PubMed:30126037
The reduced tau pathology corresponded with 60% lower Cdkn2a expression (P = 0.0041, Figure 4a), decreased SASP (Figure S4) and decreased brain atrophy (tauNFT-Mapt0/0: 0.4058 ± 0.009 versus age-matched tauNFT Maptwt/wt: 0.3451 ± 0.0116; 17.5% difference, P = 0.0143, Figure 4b) PubMed:30126037
In 15-month-old mice with heavy Abeta deposition and phosphorylated tau, but lacking NFT pathology (Orr et al., 2014), Cdkn2a expression was not elevated (Figure 4e). These data indicate that Cdkn2a expression was neither a response to general protein accumulation, nor to pre-NFT tau pathology, but instead required the presence of NFTs PubMed:30126037
Moreover, Cdkn2a was expressed at levels 2.7- and 2.6-fold higher in tauNFT than CTL and tauWT, respectively (P = 0.0303 and P = 0.0352, respectively; Figure 1g); this effect was replicated in an independent mouse cohort (P = 0.0016, Figure S1g) PubMed:30126037
Further, when plotted against brain weight, Cdkn2a expression was a strong predictor of brain atrophy across mouse lines (P < 0.0001, R2 = 0.5615; Figure 4f) PubMed:30126037
Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice PubMed:30126037
Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice PubMed:30126037
Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice PubMed:30126037
Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice PubMed:30126037
Further, when plotted against brain weight, Cdkn2a expression was a strong predictor of brain atrophy across mouse lines (P < 0.0001, R2 = 0.5615; Figure 4f) PubMed:30126037
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.