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Neurobiology of Disease

Protein links to Alzheimer’s markers differ by gene variant

An observational analysis of 115 veterans aged 50–76 without cognitive impairment found different links between immune signaling and Alzheimer’s-related markers depending on a gene variant.

Paper by Aimee K. Johnson, Carol Ann Van Hulle, Hannah Zylstra, 10 more authorsCynthia M. Carlsson · University of Wisconsin–Madison
Fig. 1. Figures 1a-g depict correlations between CX3CL1 and AD biomarkers with their ratios in APOE4− carriers.
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Fig. 1. Figures 1a-g depict correlations between CX3CL1 and AD biomarkers with their ratios in APOE4− carriers.Figures 1a-g depict correlations between CX3CL1 and AD biomarkers with their ratios in APOE4− carriers.Johnson et al.
Cohort study of 115 peopleMechanisms

Registered NCT02719327

Stake: An author holds shares in CERimmune Therapeutics. An author holds patents with Bioventix.

Edited by Boris Djordjevic · AgingResearch.News

Paper
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An observational study analyzed fluid surrounding the brain and spinal cord from 115 cognitively unimpaired veterans aged 50–76. Researchers used baseline samples collected before participants received an investigational drug in a separate trial.

They compared carriers of APOE ε4, a gene variant, with non-carriers. In statistical models, MMP-9, a protein-cutting enzyme, accounted for associations between CX3CL1, a protein involved in signaling by brain immune cells, and Alzheimer’s-related markers. This pattern appeared only in carriers, across three ratios involving amyloid and tau, proteins measured as markers of Alzheimer’s disease. CX3CL1 also correlated with a combined measure of inflammation-promoting proteins in carriers, but with a combined measure of inflammation-limiting proteins in non-carriers.

Why it matters

The authors suggest that immune-system dysregulation related to Alzheimer’s disease may occur even in carriers of this gene variant who have no cognitive impairment.

Caveats

This cross-sectional analysis cannot establish that either protein caused changes in Alzheimer’s-related markers. Participants were Veterans Affairs–eligible veterans aged 50–76 without cognitive impairment; the findings do not establish the same relationships in people with cognitive impairment or outside that age range.

From the paper

Limitation

The sample size used for this study is small and results should be considered preliminary.

Limitations

Quoted word for word from the full text on PubMed Central.

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