Kappa/Lambda light-chain typing in Alzheimer’s Disease

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Abstract

Background: Alzheimer's disease is a progressive neurodegenerative disorder characterized by memory loss and cognitive impairment. The diagnosis of Alzheimer's disease according to symptomatic events is still a puzzling task. Developing a biomarker-based, low-cost, and high-throughput test, readily applicable in clinical laboratories, dramatically impacts the rapid and reliable detection of the disease.

Objective: This study aimed to develop an accurate, sensitive, and reliable screening tool for diagnosing Alzheimer's disease, which can significantly reduce the cost and time of existing methods.

Methods: We have employed a MALDI-TOF-MS-based methodology combined with a microaffinity chromatography enrichment approach using affinity capture resins to determine serum kappa (κ) and lambda (λ) light chain levels in control and patients with AD.

Results: We observed a statistically significant difference in the kappa light chain over lambda light chain (κLC/λLC) ratios between patients with AD and controls (mean difference -0,409; % 95 CI:- 0.547 to -0.269; p<0.001). Our method demonstrated higher sensitivity (100.00%) and specificity (71.43%) for discrimination between AD and controls.

Conclusion: We have developed a high-throughput screening test with a novel sample enrichment method for determining κLC/λLC ratios associated with AD diagnosis. Following further validation, we believe our test has the potential for clinical laboratories.

Keywords: Alzheimer's disease, MALDI-TOF-MS, screening tool, microaffinity chromatography, affinity capture resins, kappa light chain, ratio, lambda light chain ratio.

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