MCP‐1 and eotaxin‐1 selectively and negatively associate with memory in MCI and Alzheimer's disease dementia phenotypes

Abstract

IntroductionMCP-1 and eotaxin-1 are encoded on chromosome 17 and have been shown to reduce hippocampal neurogenesis in mice. We investigated whether these chemokines selectively associate with memory in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia.MethodsMCP-1 and eotaxin-1 were assayed in controls, MCI, and AD dementia patients with varying phenotypes (n = 171). A subset of 55 individuals had magnetic resonance imaging (MRI) scans available. Composite scores for cognitive variables were created, and medial temporal lobe volumes were obtained.ResultsAn interaction was noted between MCP-1 and eotaxin-1, such that deleterious associations with memory were seen when both chemokines were elevated. These associations remained significant after adding APOE genotype and comparison (non-chromosome 17) chemokines into the model. These chemokines predicted left medial temporal lobe volume and were not related to other cognitive domains.DiscussionThese results suggest a potentially selective role for MCP-1 and eotaxin-1 in memory dysfunction in the context of varied MCI and AD dementia phenotypes.

Circulating levels of monocyte chemoattractant protein‐1 as a potential measure of biological age in mice and frailty in humans

“…Senescence‐associated secretory phenotype can promote secondary senescence in healthy cells (Coppe, Desprez, Krtolica & Campisi, ), and senescent cells have been demonstrated to promote aging and age‐related disease (Baker et al., , ; Zhu et al., ). Circulating levels of MCP‐1 are increased in patients with renal disease (Akdogan et al., ), cognitive impairment and Alzheimer's disease (Bettcher et al., ), atherosclerosis and cardiovascular disease (Deo et al., ). Monocyte chemoattractant protein‐1 is considered to be a marker of “inflammaging,” defined as chronic sterile inflammation that is associated with numerous age‐related diseases (Franceschi & Campisi, ).…”

Association between plasma CCL11 (eotaxin-1) and cognitive status in older adults: Differences between rural and urban dwellers

“…The relationship between measures of cognition and CCL11 has not been widely explored. Small studies in patients diagnosed with MCI or AD have generated mixed findings (Bettcher et al, 2016;Leung et al, 2013;Westin et al, 2012). Bettcher et al found that higher levels of CCL11 in combination with MCP-1 predict worse memory functions in MCI and AD phenotypes (Bettcher et al, 2016), whereas Leung and co-workers reported significantly higher levels of CCL11 in patients with AD compared to those with MCI (Leung et al, 2013).…”

“…More recently, circulating levels of CCL11 have been shown to rise with normal human ageing (Bradburn et al;Shurin et al, 2007;Villeda et al, 2011) and in neurodegenerative diseases (Huber et al, 2018). In particular, small studies have linked higher blood levels of CCL11 with Alzheimer's disease (AD) (Choi et al, 2008) and with memory deficits in older adults diagnosed with mild cognitive impairment (MCI) and AD dementia phenotypes (Bettcher et al, 2016). In contrast, high CCL11 levels were found to correlate with a delayed age at onset in AD (Lalli et al, 2015) suggesting a complex role of this chemokine in neurodegeneration.…”

Introduction to special issue on Advances in blood‐based biomarkers of Alzheimer's disease

“…In this issue, Bettcher et al. [9] study MCP‐1 and eotaxin‐1 levels among controls, MCI, and AD cases in relation to memory abilities as well as medial temporal lobe volumes. When both chemokines were elevated, memory scores were specifically poorer.…”

“…Recent work has begun to study the link between biomarker levels and specific clinically relevant outcomes (e.g., memory scores, structural MRI outcomes) [8]. In this issue, Bettcher et al [9] study MCP-1 and eotaxin-1 levels among controls, MCI, and AD cases in relation to memory abilities as well as medial temporal lobe volumes. When both chemokines were elevated, memory scores were specifically poorer.…”