Urinary Cytokines as Potential Biomarkers of Mild Cognitive Impairment and Alzheimer’s Disease: A Pilot Study

Author:

Saiyed Nazia1,Yilmaz Ali12,Vishweswariah Sangeetha1,Maiti Amit K.3,Ustun Ilyas4,Bartolone Sarah5,Brown-Hughes Travonia6,Thorpe Roland J.7,Osentoski Tammy8,Ruff Stacey9,Pai Amita9,Maddens Michael9,Imam Khaled9,Graham Stewart F.12

Affiliation:

1. Beaumont Research Institute, Metabolomics Department, Royal Oak, MI, USA

2. Oakland University-William Beaumont School of Medicine, Rochester, MI, USA

3. Department of Genetics and Genomics, Mydnavar, Southfield, MI, USA

4. College of Computing and Digital Media, DePaul University, Chicago, IL, USA

5. Department of Urology, Beaumont Research Institute, Royal Oak, MI, USA

6. School of Pharmacy, Hampton University, Hampton, VA, USA

7. Department of Health, Behavior, and Society, Program for Research on Men’s Health, Hopkins Center for Health Disparities Solutions, Johns Hopkins Alzheimer’s Disease Resource Center for Minority Aging Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

8. Department of Alzheimer’s Research, Beaumont Health, Royal Oak, MI, USA

9. Beaumont Health, Geriatric Medicine, Berkley, MI, USA

Abstract

Background: Alzheimer’s disease (AD) is the most common form of dementia, accounting for 80% of all cases. Mild cognitive impairment (MCI) is a transitional state between normal aging and AD. Early detection is crucial, as irreversible brain damage occurs before symptoms manifest. Objective: This study aimed to identify potential biomarkers for early detection of AD by analyzing urinary cytokine concentrations. We investigated 37 cytokines in AD, MCI, and cognitively normal individuals (NC), assessing their associations with AD development. Methods: Urinary cytokine concentrations were measured in AD (n = 25), MCI (n = 25), and NC (n = 26) patients. IL6ST and MMP-2 levels were compared between AD and NC, while TNFRSF8, IL6ST, and IL-19 were assessed in AD versus MCI. Diagnostic models distinguished AD from NC, and in-silico analysis explored molecular mechanisms related to AD. Results: Significant perturbations in IL6ST and MMP-2 concentrations were observed in AD urine compared to NC, suggesting their potential as biomarkers. TNFRSF8, IL6ST, and IL-19 differed significantly between AD and MCI, implicating them in disease progression. Diagnostic models exhibited promising performance (AUC: 0.59–0.79, sensitivity: 0.72–0.80, specificity: 0.56–0.78) in distinguishing AD from NC. In-silico analysis revealed molecular insights, including relevant non-coding RNAs, microRNAs, and transcription factors. Conclusion: This study establishes significant associations between urinary cytokine concentrations and AD and MCI. IL6ST, MMP-2, TNFRSF8, IL6ST, and IL-19 emerge as potential biomarkers for early detection of AD. In-silico analysis enhances understanding of molecular mechanisms in AD. Further validation and exploration of these biomarkers in larger cohorts are warranted to assess their clinical utility.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Neuroscience

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