Serum Levels of Clusterin, PKR, and RAGE Correlate with Amyloid Burden in Alzheimer’s Disease

Article type: Research Article

Authors: Monllor, Paloma^{a; 1} | Giraldo, Esther^{b; c; 1} | Badia, Mari-Carmen^d | de la Asuncion, Jose Garcia^d | Alonso, Maria-Dolores^d | Lloret, Ana^{a; *} | Vina, Jose^a

Affiliations: [a] Freshage Research Group, Department of Physiology, University of Valencia, CIBERFES-ISCIII, INCLIVA, Valencia, Spain | [b] Department of Biotechnology, Universitat Politècnica de València, Valencia, Spain | [c] Principe Felipe Research Center, Valencia, Spain | [d] Hospital Clinico Universitario de Valencia, Valencia, Spain

Correspondence: [*] Correspondence to: Ana Lloret, Freshage Research Group, Department of Physiology, University of Valencia, CIBERFES-ISCIII, INCLIVA, Valencia, Spain. Tel.: +34 963864154; Fax: +34 963864642; E-mail: ana.lloret@uv.es.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Alzheimer’s disease (AD) is the most common form of dementia and biomarkers are essential to help in the diagnosis of this disease. Image techniques and cerebrospinal fluid (CSF) biomarkers are limited in their use because they are expensive or invasive. Thus, the search for blood-borne biomarkers is becoming central to the medical community. Objective:The main objective of this study is the evaluation of three serum proteins as potential biomarkers in AD patients. Methods:We recruited 27 healthy controls, 19 mild cognitive impairment patients, and 17 AD patients. Using the recent A/T/N classification we split our population into two groups (AD and control). We used ELISA kits to determine Aβ42, tau, and p-tau in CSF and clusterin, PKR, and RAGE in serum. Results:The levels of serum clusterin, PKR, and RAGE were statistically different in the AD group compared to controls. These proteins showed a statistically significant correlation with CSF Aβ42. So, they were selected to generate an AD detection model showing an AUC-ROC of 0.971 (CI 95%, 0.931–0.998). Conclusion:The developed model based on serum biomarkers and other co-variates could reflect the AD core pathology. So far, not one single blood-biomarker has been described, with effectiveness offering high sensitivity and specificity. We propose that the complexity of AD pathology could be reflected in a set of biomarkers also including clinical features of the patients.

Keywords: Alzheimer’s disease, biomarkers, clusterin, dementia, RAGE (receptor for advanced glycation end products), ROC curve

DOI: 10.3233/JAD-201443

Journal: Journal of Alzheimer's Disease, vol. 80, no. 3, pp. 1067-1077, 2021