Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline.

Autor: Duggan MR; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA., Peng Z; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA., Sipilä PN; Clinicum, Department of Public Health, University of Helsinki, Helsinki, Finland.; Finnish Institute of Occupational Health, Helsinki, Finland., Lindbohm JV; Clinicum, Department of Public Health, University of Helsinki, Helsinki, Finland.; Broad Institute of the MIT and Harvard University, The Klarman Cell Observatory, Cambridge, MA, USA.; Brain Sciences, University College London, London, UK., Chen J; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA., Lu Y; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Davatzikos C; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA., Erus G; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA., Hohman TJ; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA., Andrews SJ; Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA., Candia J; Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA., Tanaka T; Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA., Joynes CM; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.; Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA., Alvarado CX; Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.; DataTecnica LLC, Washington, DC, USA., Nalls MA; Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.; DataTecnica LLC, Washington, DC, USA.; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA., Cordon J; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA., Daya GN; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA., An Y; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA., Lewis A; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Moghekar A; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Palta P; Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Coresh J; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA., Ferrucci L; Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA., Kivimäki M; Clinicum, Department of Public Health, University of Helsinki, Helsinki, Finland.; Brain Sciences, University College London, London, UK., Walker KA; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. keenan.walker@nih.gov.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2024 Sep; Vol. 4 (9), pp. 1263-1278. Date of Electronic Publication: 2024 Aug 14.
DOI: 10.1038/s43587-024-00682-4
Abstrakt: Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe. We identified 260 out of 942 immunologically relevant proteins in plasma that were differentially expressed in individuals with an infection history. Of the infection-related proteins, 35 predicted volumetric changes in brain regions vulnerable to infection-specific atrophy. Several of these proteins, including PIK3CG, PACSIN2, and PRKCB, were related to cognitive decline and plasma biomarkers of dementia (Aβ 42/40 , GFAP, NfL, pTau-181). Genetic variants that influenced expression of immunologically relevant infection-related proteins, including ITGB6 and TLR5, predicted brain volume loss. Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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