Background
Inflammatory protein biomarkers induced by immune responses have been associated with cognitive decline and the pathogenesis of Alzheimer’s disease (AD). A group from Boston University School of Public Health used the Olink® Target 96 Inflammation panel to examine circulating inflammatory proteins in a cohort of 708 individuals who were followed for up to 20 years to look for changes in cognitive function, all-cause dementia, or AD dementia. Plasma samples were taken at baseline and protein levels compared to the subsequent neurological outcomes measured using the well-characterized Framingham Heart Study Offspring cohort.
Outcome
Previous studies in the same cohort had shown that chronic peripheral inflammation measured with C-reactive protein (CRP) increased the risk for dementia and AD dementia, but only in subjects with the APOE ε4 genotype, hence the subjects in the present study were also stratified by APOE genotypes. Significant associations were seen between 68 proteins and the different types of cognitive domain scores measured. Moreover, IL10, LIF-R, TWEAK, CCL19, IL-17C, MCP-4, and TGF-alpha all associated with more than one of the tested cognitive domains. The stratified analysis suggested differences in protein effects between APOE ε2 and ε4 carriers, with most ε4 carrier associations with the executive function and memory domains, and most ε2 associations with the visuospatial domain. Higher levels of TNFB and CDCP1 were associated with an increased risk of incident all-cause and AD dementia.
One intriguing observation was that most of the inflammatory proteins associated with cognitive scores were not associated with incident all-cause dementia or AD dementia, and most dementia-associated proteins did not correlate with cognitive scores. The authors suggested that cross-sectional measures of cognition at the time of blood draw reflect lifelong or mid-to-late life cognitive processes that may be quite different from cognitive impairment and dementia from neurodegeneration.
Overall, these data confirm the association of multiple inflammatory biomarkers with incident dementia and identified several proteins associated specifically with non-dementia cognitive function changes. Some of the proteins identified could prove to be important for future therapeutic interventions to prevent and treat cognitive decline.
