The influence of insulin resistance on CSF and plasma biomarkers of Alzheimer’s pathology

Journal article

Background: Insulin resistance (IR) has previously been associated with an increased risk of developing Alzheimer’s disease (AD), though the relationship between IR and AD is not yet clear. Here, we examined the influence of IR on AD by using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in cognitively healthy men, and to characterize the shared protein signatures between IR and AD.

Methods: 58 cognitively healthy men, 28 IR and 30 non-IR (age and APOE ε4 matched), were drawn from the METSIM (Metabolic Syndrome in Men) study in Kuopio, Finland. CSF AD biomarkers (amyloid β-peptide (Aβ), total tau and tau phosphorylated at the Thr181 epitope) were examined with respect to IR. Targeted proteomics using ELISA and Luminex xMAP assays were performed to assess the influence of IR on previously identified CSF and plasma protein biomarker candidates of AD pathology. Furthermore CSF and plasma SOMAscan was performed to discover proteins that associate with IR and CSF AD biomarkers.

Results: CSF AD biomarkers did not differ between IR and non-IR groups, though plasma insulin correlated with CSF Aβ/tau across the whole cohort. 200 CSF and 487 plasma proteins were differentially expressed between IR and non-IR subjects, and significantly enriched pathways, many of which have been previously implicated in AD, were identified. CSF and plasma proteins significantly associated with CSF AD biomarkers were also discovered, and those sensitive to both IR and AD were identified.

Conclusions: This data indicates that IR is not directly related to the level of CSF AD pathology in cognitively healthy men. Proteins that associated with both AD and IR are potential markers indicative of shared pathology.

Authors: Westwood, S; Liu, B; Baird, A; Anand, S; Nevado-Holgado, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: Alzheimer's Research and Therapy
• Volume: 9
• Issue: 31
• Publication date: 2017-04-26
• Acceptance date: 2017-03-08
• DOI: 10.1186/s13195-017-0258-6
• ISSN: 1758-9193
• Keywords: Alzheimer’s disease; proteomics; plasma biomarkers; cerebrospinal fluid biomarkers; insulin resistance; diabetes mellitus