APA
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Duggan, M. R., Peng, Z., Sipilä, P., Lindbohm, J. V., Chen, J., Lu, Y., … Walker, K. A. (2024). Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline. Nature Aging.
Chicago/Turabian
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Duggan, Michael R., Zhongsheng Peng, P. Sipilä, Joni V. Lindbohm, Jingsha Chen, Yifei Lu, C. Davatzikos, et al. “Proteomics Identifies Potential Immunological Drivers of Postinfection Brain Atrophy and Cognitive Decline.” Nature Aging (2024).
MLA
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Duggan, Michael R., et al. “Proteomics Identifies Potential Immunological Drivers of Postinfection Brain Atrophy and Cognitive Decline.” Nature Aging, 2024.
BibTeX Click to copy
@article{michael2024a,
title = {Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline},
year = {2024},
journal = {Nature Aging},
author = {Duggan, Michael R. and Peng, Zhongsheng and Sipilä, P. and Lindbohm, Joni V. and Chen, Jingsha and Lu, Yifei and Davatzikos, C. and Erus, G. and Hohman, T. and Andrews, Shea J and Candia, J. and Tanaka, Toshiko and Joynes, Cassie and Alvarado, Chelsea X. and Nalls, Mike A. and Cordon, Jenifer and Daya, Gulzar N. and An, Yang and Lewis, Alexandria and Moghekar, A. and Palta, P. and Coresh, J. and Ferrucci, L. and Kivimäki, Mika and Walker, Keenan A.}
}
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 (Aβ42/40, 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. This study reveals how infections that increase long-term dementia risk can contribute to longitudinal brain volume loss and regulate immunological proteins in plasma, and which of these proteins may drive infection-specific neurodegeneration.