Integration across biophysical scales identifies molecular and cellular correlates of person-to-person variability in human brain connectivity.

Autor: Ng B; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA., Tasaki S; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA., Greathouse KM; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA., Walker CK; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA., Zhang A; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA., Covitz S; Penn/CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, PA, USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.; Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA, USA., Cieslak M; Penn/CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, PA, USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.; Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA, USA., Weber AJ; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA., Adamson AB; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA., Andrade JP; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA., Poovey EH; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA., Curtis KA; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA., Muhammad HM; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA., Seidlitz J; Penn/CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, PA, USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.; Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA, USA.; Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Satterthwaite T; Penn/CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, PA, USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.; Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA, USA., Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA., Seyfried NT; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA., Vogel J; Penn/CHOP Lifespan Brain Institute, University of Pennsylvania, Philadelphia, PA, USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.; Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA, USA.; Department of Clinical Science, Malmö, SciLifeLab, Lund University, Lund, Sweden., Gaiteri C; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. gaiteri@gmail.com.; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA. gaiteri@gmail.com., Herskowitz JH; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA. jhersko@uab.edu.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2024 Nov; Vol. 27 (11), pp. 2240-2252. Date of Electronic Publication: 2024 Oct 31.
DOI: 10.1038/s41593-024-01788-z
Abstrakt: Brain connectivity arises from interactions across biophysical scales, ranging from molecular to cellular to anatomical to network level. To date, there has been little progress toward integrated analysis across these scales. To bridge this gap, from a unique cohort of 98 individuals, we collected antemortem neuroimaging and genetic data, as well as postmortem dendritic spine morphometric, proteomic and gene expression data from the superior frontal and inferior temporal gyri. Through the integration of the molecular and dendritic spine morphology data, we identified hundreds of proteins that explain interindividual differences in functional connectivity and structural covariation. These proteins are enriched for synaptic structures and functions, energy metabolism and RNA processing. By integrating data at the genetic, molecular, subcellular and tissue levels, we link specific biochemical changes at synapses to connectivity between brain regions. These results demonstrate the feasibility of integrating data from vastly different biophysical scales to provide a more comprehensive understanding of brain connectivity.
(© 2024. The Author(s).)
Databáze: MEDLINE
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