1. Omics‐derived biological modules reflect metabolic brain changes in Alzheimer's disease.
- Author
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Povala, Guilherme, De Bastiani, Marco Antônio, Bellaver, Bruna, Ferreira, Pamela C. L., Ferrari‐Souza, João Pedro, Lussier, Firoza Z., Souza, Diogo O., Rosa‐Neto, Pedro, Pascoal, Tharick A., Zatt, Bruno, and Zimmer, Eduardo R.
- Abstract
INTRODUCTION: Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive. METHODS: Here, we integrated [18F]FDG‐PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel‐wise linear regression analysis. RESULTS: Our results showed that multiple transcriptomic modules are associated with brain [18F]FDG‐PET metabolism, with the top hits being a protein serine/threonine kinase activity gene cluster (peak‐t(223) = 4.86, P value < 0.001) and zinc‐finger–related regulatory units (peak‐t(223) = 3.90, P value < 0.001). DISCUSSION: By integrating transcriptomics with PET imaging data, we identified that serine/threonine kinase activity–associated genes and zinc‐finger–related regulatory units are highly associated with brain metabolic changes in AD. Highlights: We conducted an integrated analysis of system‐based transcriptomics and fluorodeoxyglucose positron emission tomography ([18F]FDG‐PET) at the voxel level in Alzheimer's disease (AD).The biological process of serine/threonine kinase activity was the most associated with [18F]FDG‐PET in the AD brain.Serine/threonine kinase activity alterations are associated with brain vulnerable regions in AD [18F]FDG‐PET.Zinc‐finger transcription factor targets were associated with AD brain [18F]FDG‐PET metabolism. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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