Neurogenetic contributions to amyloid beta and tau spreading in the human cortex
| Autor: | Jorge Sepulcre, Georges El-Fakhri, Heidi I.L. Jacobs, Laura Ortiz-Terán, Hyun-Sik Yang, Quanzheng Li, Michel J. Grothe, Keith A. Johnson, Bernard Hanseeuw, Federico d'Oleire Uquillas, Ibai Diez, Reisa A. Sperling |
|---|---|
| Přispěvatelé: | UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, UCL - SSS/IONS - Institute of NeuroScience |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male genetics [Transcriptome] genetics [Alzheimer Disease] diagnostic imaging [Protein Aggregation Pathological] Transcriptome pathology [Alzheimer Disease] 0302 clinical medicine Gene expression diagnostic imaging [Cerebral Cortex] genetics [Amyloid beta-Peptides] Axon Cerebral Cortex biology Brain General Medicine Human brain medicine.anatomical_structure Female metabolism [Alzheimer Disease] Amyloid beta metabolism [Amyloid beta-Peptides] tau Proteins Protein Aggregation Pathological General Biochemistry Genetics and Molecular Biology 03 medical and health sciences pathology [Protein Aggregation Pathological] Alzheimer Disease mental disorders medicine Humans genetics [Protein Aggregation Pathological] ddc:610 diagnostic imaging [Brain] Amyloid beta-Peptides Lipid metabolism Pet imaging Lipid Metabolism metabolism [tau Proteins] genetics [tau Proteins] 030104 developmental biology Positron-Emission Tomography genetics [Lipid Metabolism] biology.protein pathology [Cerebral Cortex] Neuroscience diagnostic imaging [Alzheimer Disease] 030217 neurology & neurosurgery |
| Zdroj: | Nature medicine 24(12), 1910-1918 (2018). doi:10.1038/s41591-018-0206-4 Nature medicine, Vol. 24, no.12, p. 1910-1918 (2018) Nature medicine, Vol. 24, no. 12, p. 1910-1918 (2018) |
| DOI: | 10.1038/s41591-018-0206-4 |
| Popis: | Tau and amyloid beta (Aβ) proteins accumulate along neuronal circuits in Alzheimer’s disease. Unraveling the genetic background for the regional vulnerability of these proteinopathies can help in understanding the mechanisms of pathology progression. To that end, we developed a novel graph theory approach and used it to investigate the intersection of longitudinal Aβ and tau positron emission tomography imaging of healthy adult individuals and the genetic transcriptome of the Allen Human Brain Atlas. We identified distinctive pathways for tau and Aβ accumulation, of which the tau pathways correlated with cognitive levels. We found that tau propagation and Aβ propagation patterns were associated with a common genetic profile related to lipid metabolism, in which APOE played a central role, whereas the tau-specific genetic profile was classified as ‘axon related’ and the Aβ profile as ‘dendrite related’. This study reveals distinct genetic profiles that may confer vulnerability to tau and Aβ in vivo propagation in the human brain. Cross-sectional and longitudinal PET imaging of amyloid beta and tau in the human brain is combined with gene expression profiles to define the interactions between Alzheimer’s disease-related pathology propagation and brain-region-specific vulnerability. |
| Databáze: | OpenAIRE |
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