Integrated transcriptomic and neuroimaging brain model decodes biological mechanisms in aging and Alzheimer’s disease
| Autor: | Yasser Iturria-Medina, Alzheimer’s Disease Neuroimaging Initiative, Felix Carbonell, Ahmed F Khan, Quadri Adewale |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Aging Disease Transcriptome 0302 clinical medicine Biology (General) Cognitive decline Brain model clinical imaging General Neuroscience Neurodegeneration neurodegeneration Brain General Medicine Alzheimer's disease Magnetic Resonance Imaging Medicine Research Article Human QH301-705.5 Science Models Neurological tau Proteins Genomics Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Atrophy Neuroimaging Alzheimer Disease medicine Humans Cognitive Dysfunction Aged Amyloid beta-Peptides General Immunology and Microbiology Genetics and Genomics medicine.disease Glucose 030104 developmental biology Positron-Emission Tomography gene expression multifactorial causal model Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | eLife eLife, Vol 10 (2021) |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.62589 |
| Popis: | Both healthy aging and Alzheimer’s disease (AD) are characterized by concurrent alterations in several biological factors. However, generative brain models of aging and AD are limited in incorporating the measures of these biological factors at different spatial resolutions. Here, we propose a personalized bottom-up spatiotemporal brain model that accounts for the direct interplay between hundreds of RNA transcripts and multiple macroscopic neuroimaging modalities (PET, MRI). In normal elderly and AD participants, the model identifies top genes modulating tau and amyloid-β burdens, vascular flow, glucose metabolism, functional activity, and atrophy to drive cognitive decline. The results also revealed that AD and healthy aging share specific biological mechanisms, even though AD is a separate entity with considerably more altered pathways. Overall, this personalized model offers novel insights into the multiscale alterations in the elderly brain, with important implications for identifying effective genetic targets for extending healthy aging and treating AD progression. |
| Databáze: | OpenAIRE |
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