Peripheral inflammation is associated with brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer’s disease
Nuanyi Liang, Kwangsik Nho, John W. Newman, Matthias Arnold, Kevin Huynh, Peter J. Meikle, Kamil Borkowski, Rima Kaddurah-Daouk, Alexandra Kueider‐Paisley, P. Murali Doraiswamy, Colette Blach, Arthur Moseley, Siamak Mahmoudiandehkhordi, Kathleen Welsh-Balmer, Brenda L. Plassman, Andrew J. Saykin, Shannon L. Risacher, Gabi Kastenmüller, Xianlin Han, Rebecca Baillie, Rob Knight, Pieter C. Dorrestein, James M. Brewer, Emeran A. Mayer, Jennifer S. Labus, Pierre Baldi, Arpana Gupta, Oliver Fiehn, Dinesh Kumar Barupal, Peter J. Meikle, Sarkis K. Mazmanian, Dan Rader, Leslie M. Shaw, Cornelia van Duijin, Najaf Amin, Alejo Nevado‐Holgado, David A. Bennett, Ranga Krishnan, Ali Keshavarzian, Robin Vogt, M. Arfan Ikram, Thomas Hankemeier, Ines Thiele, Cory C. Funk, Priyanka Baloni, Wei Jia, David S. Wishart, Roberta Dı́az Brinton, Lindsay A. Farrer, Rhoda Au, Wendy Qiu, Peter Würtz, Therese Koal, Anna Greenwood, Jan Krumsiek, Karsten Suhre, John W. Newman, Ivan Hernandez, Tatania Foroud, Frank M. Sacks
Abstract
Inflammation is an important factor in Alzheimer's disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman's correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer's Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman's correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3-9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention.