Dataset Information

The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer's pathology.

ABSTRACT: Insulin resistance (IR) has previously been associated with an increased risk of developing Alzheimer's disease (AD), although the relationship between IR and AD is not yet clear. Here, we examined the influence of IR on AD using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in cognitively healthy men. We also aimed to characterise the shared protein signatures between IR and AD.Fifty-eight cognitively healthy men, 28 IR and 30 non-IR (age and APOE ?4 matched), were drawn from the Metabolic Syndrome in Men study in Kuopio, Finland. CSF AD biomarkers (amyloid ?-peptide (A?), 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.CSF AD biomarkers did not differ between IR and non-IR groups, although plasma insulin correlated with CSF A?/tau across the whole cohort. In total, 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.These data indicate 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.

SUBMITTER: Westwood S

PROVIDER: S-EPMC5405532 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer's pathology.

Westwood Sarah S Liu Benjamine B Baird Alison L AL Anand Sneha S Nevado-Holgado Alejo J AJ Newby Danielle D Pikkarainen Maria M Hallikainen Merja M Kuusisto Johanna J Streffer Johannes R JR Novak Gerald G Blennow Kaj K Andreasson Ulf U Zetterberg Henrik H Smith Ulf U Laakso Markku M Soininen Hilkka H Lovestone Simon S

Alzheimer's research & therapy 20170426 1

<h4>Background</h4>Insulin resistance (IR) has previously been associated with an increased risk of developing Alzheimer's disease (AD), although the relationship between IR and AD is not yet clear. Here, we examined the influence of IR on AD using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in cognitively healthy men. We also aimed to characterise the shared protein signatures between IR and AD.<h4>Methods</h4>Fifty-eight cognitively healthy men, 28 IR and 30 non-IR (ag ...[more]

PMID: 28441961

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Project description:Previous studies have suggested a correlation between elevated levels of β2-microglobulin (B2M) and cognitive impairment. However, the existing evidence is insufficient to establish a conclusive relationship. This study aims to analyze the link of plasma B2M to cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers and cognition. To track the dynamics of plasma B2M in preclinical AD, 846 cognitively healthy individuals in the Chinese Alzheimer's Biomarker and LifestylE (CABLE) cohort were divided into four groups (suspected non-AD pathology [SNAP], 2, 1, 0) according to the NIA-AA criteria. Multiple linear regression models were employed to examine the plasma B2M's relationship with cognitive and CSF AD biomarkers. Causal mediation analysis was conducted through 10,000 bootstrapped iterations to explore the mediating effect of AD pathology on cognition. We found that the levels of plasma B2M were increased in stages 1 (P = 0.0007) and 2 (P < 0.0001), in contrast to stage 0. In total participants, higher levels of B2M were associated with worse cognitive performance (P = 0.006 for MMSE; P = 0.012 for MoCA). Moreover, a higher level of B2M was associated with decreases in Aβ1-42 (P < 0.001) and Aβ1-42/Aβ1-40 (P = 0.015) as well as increases in T-tau/Aβ1-42 (P < 0.001) and P-tau/Aβ1-42 (P < 0.001). The subgroup analysis found B2M correlated with Aβ1-42 in non-APOE ε4 individuals (P < 0.001) but not in APOE ε4 carriers. Additionally, the link between B2M and cognition was partially mediated by Aβ pathology (percentage: 8.6 to 19.3%), whereas tau pathology did not mediate this effect. This study demonstrated the association of plasma B2M with CSF AD biomarkers as well as a possible important role of Aβ pathology in the association between B2M and cognitive impairment, particularly in cognitively normal individuals. The results indicated that B2M could be a potential biomarker for preclinical AD and might have varied functions throughout various stages of preclinical AD progression.

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Dataset Information

The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer's pathology.

Publications

The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer's pathology.

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