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Plasma proteins related to inflammatory diet predict future cognitive impairment
Journal article   Open access   Peer reviewed

Plasma proteins related to inflammatory diet predict future cognitive impairment

Michael R Duggan, Lauren Butler, Zhongsheng Peng, Gulzar N Daya, Abhay Moghekar, Yang An, Stephen R Rapp, Kathleen M Hayden, Aladdin H Shadyab, Ginny Natale, …
Molecular psychiatry, Vol.28(4), pp.1599-1609
04/2023
DOI: 10.1038/s41380-023-01975-7
PMCID: PMC10208977
PMID: 36737481
url
https://doi.org/10.1038/s41380-023-01975-7View
Published (Version of record) Open Access

Abstract

Dysregulation of the immune system and dietary patterns that increase inflammation can increase the risk for cognitive decline, but the mechanisms by which inflammatory nutritional habits may affect the development of cognitive impairment in aging are not well understood. To determine whether plasma proteins linked to inflammatory diet predict future cognitive impairment, we applied high-throughput proteomic assays to plasma samples from a subset (n = 1528) of Women's Health Initiative Memory Study (WHIMS) participants (mean [SD] baseline age, 71.3 [SD 3.8] years). Results provide insights into how inflammatory nutritional patterns are associated with an immune-related proteome and identify a group of proteins (CXCL10, CCL3, HGF, OPG, CDCP1, NFATC3, ITGA11) related to future cognitive impairment over a 14-year follow-up period. Several of these inflammatory diet proteins were also associated with dementia risk across two external cohorts (ARIC, ESTHER), correlated with plasma biomarkers of Alzheimer's disease (AD) pathology (Aβ ) and/or neurodegeneration (NfL), and related to an MRI-defined index of neurodegenerative brain atrophy in a separate cohort (BLSA). In addition to evaluating their biological relevance, assessing their potential role in AD, and characterizing their immune-tissue/cell-specific expression, we leveraged published RNA-seq results to examine how the in vitro regulation of genes encoding these candidate proteins might be altered in response to an immune challenge. Our findings indicate how dietary patterns with higher inflammatory potential relate to plasma levels of immunologically relevant proteins and highlight the molecular mediators which predict subsequent risk for age-related cognitive impairment.

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