1. Plasma proteins related to inflammatory diet predict future cognitive impairment
- Author
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Duggan, Michael R, Butler, Lauren, Peng, Zhongsheng, Daya, Gulzar N, Moghekar, Abhay, An, Yang, Rapp, Stephen R, Hayden, Kathleen M, Shadyab, Aladdin H, Natale, Ginny, Liu, Longjian, Snetselaar, Linda, Moaddel, Ruin, Rebholz, Casey M, Sullivan, Kevin, Ballantyne, Christie M, Resnick, Susan M, Ferrucci, Luigi, and Walker, Keenan A
- Subjects
Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Neurosciences ,Neurodegenerative ,Dementia ,Acquired Cognitive Impairment ,Brain Disorders ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Nutrition ,Aging ,Alzheimer's Disease ,Clinical Research ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,Detection ,screening and diagnosis ,4.1 Discovery and preclinical testing of markers and technologies ,Neurological ,Inflammatory and immune system ,Humans ,Female ,Aged ,Proteomics ,Alzheimer Disease ,Cognitive Dysfunction ,Diet ,Blood Proteins ,Biomarkers ,tau Proteins ,Amyloid beta-Peptides ,Antigens ,Neoplasm ,Cell Adhesion Molecules ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Biological psychology ,Clinical and health psychology - 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 (Aβ42/40) 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.
- Published
- 2023