Serum Amyloidogenic Nanoplaques and Cytokines in Alzheimer’s Disease: Pilot Study in a Small Naturalistic Memory Clinic Cohort

Abstract

Background: Neuroinflammation is a central component of Alzheimer’s disease (AD) and correlates closely with amyloid pathology. Markers of inflammation such as cytokines, and amyloidogenic aggregates, so-called nanoplaques, are both promising biomarker candidates for AD. We have previously shown that there is a relationship between the levels of nanoplaques and cytokines in cerebrospinal fluid, but it is unknown whether this association extends to serum. Objective: Investigate in a naturalistic memory clinic cohort whether the associations between nanoplaques and cytokines in the cerebrospinal fluid extends to serum. Methods: We collected serum from 49 patients assessed for cognitive complaints at the Oslo University Hospital Memory Clinic (15 with clinical AD). We assessed the levels of serum nanoplaques with the novel Thioflavin-T fluorescence correlation spectroscopy (ThT-FCS) assay. Serum levels of nine cytokines (eotaxin-1, granulocyte colony-stimulating factor [G-CSF], interleukin [IL]-6, IL-7, IL-8, monocyte chemoattractant protein-1 (MCP-1), gamma induced protein 10 (IP-10), macrophage inflammatory protein [MIP]-1α, and MIP-1β) were quantified with a multiplex assay and read on a Luminex IS 200 instrument. Results: Serum nanoplaques were not increased in clinical AD patients compared to non-AD memory clinic patients and nanoplaques were not associated with any cytokines. The cytokines IL-8 and G-CSF were increased in patients with clinical AD compared to non-AD patients. Conclusion: In this small pilot study, serum nanoplaques were not associated with serum cytokines. Nanoplaque levels could not be used to separate clinical AD patients from non-AD patients in this unselected memory clinic cohort.

Alteration of Blood Immune Biomarkers in MCI Patients with Different APOE Genotypes after Cognitive Training: A 1 Year Follow-Up Cohort Study

“…IL-8 was also associated with the accumulation of pathological proteins characteristic of AD [88,89]. Lower levels of Aβ40 and Aβ42 and higher levels of IL-8 were associated with more severe cognitive decline [88][89][90].…”

“…IL-8 was also associated with the accumulation of pathological proteins characteristic of AD [88,89]. Lower levels of Aβ40 and Aβ42 and higher levels of IL-8 were associated with more severe cognitive decline [88][89][90]. Positron emission tomography (PET) research indicated negative associations of Aβ with cerebrospinal fluid (CSF) IL-8 levels in the areas where early Aβ accumulation occurs (in the lateral and medial frontal lobes) [91].…”

Methods to Discover and Validate Biofluid-Based Biomarkers in Neurodegenerative Dementias

“…There are also examples of how predefined cytokine panels have been used for serum analysis in the context of PD ( 79 ) and complement factors in plasma in search for FTD-associated profiles in samples from the GENFI consortium ( 80 ). In one study, a custom-designed panel was assembled based on initial analysis of a predefined set of proteins and evaluated in serum samples from an AD cohort ( 81 ). The single binder assay has been applied to perform large-scale analysis of both CSF and plasma/serum in the context of AD ( 82 , 83 ), FTD ( 84 , 85 ), ALS ( 86 ), and for the analysis of CSF protein levels in cognitively healthy individuals ( 87 ).…”