Peripheral Blood Biomarkers Coupled with the Apolipoprotein E4 Genotype Are Strongly Associated with Semantic and Episodic Memory Impairments in Elderly Subjects with Amnestic Mild Cognitive Impairment and Alzheimer’s Disease

Article type: Research Article

Authors: Supasitthumrong, Thitiporn^a | Tunvirachaisakul, Chavit^a | Aniwattanapong, Daruj^a | Tangwongchai, Sookjaroen^a | Chuchuen, Phenphichcha^a | Tawankanjanachot, Itthipol^a | Snabboon, Thiti^b | Hemrungrojn, Solaphat^a | Carvalho, Andre F.^{c; d} | Maes, Michael^{a; e; f; *}

Affiliations: [a] Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand | [b] Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand | [c] Department of Psychiatry, University of Toronto, Toronto, ON, Canada | [d] Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada | [e] Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria | [f] IMPACT Strategic Research Center, Deakin University, Geelong, Australia

Correspondence: [*] Correspondence to: Prof. Dr. Michael Maes, MD, PhD, IMPACT Strategic Research Center Barwon Health, Deakin University, Geelong, VIC, Australia. E-mail: [email protected].

Abstract: Background:The Apolipoprotein E4 (ApoE4) genotype is strongly associated with Alzheimer’s disease (AD), although the presence of the ApoE4 allele alone is not sufficient to explain AD. The pathophysiology of amnestic mild cognitive impairment (aMCI) remains unclear. Objective:This study aims to examine associations between peripheral blood biomarkers coupled with ApoE4 and episodic and semantic memory. Methods:The CERAD battery was completed and various biomarkers were assayed in 60 subjects with aMCI, 60 with AD, and 62 healthy controls. Results:Deficits in semantic and episodic memory were significantly predicted by anion gap and bicarbonate, albumin, and glucose coupled with ApoE4. Furthermore, these peripheral biomarkers interacted with ApoE to predict greater memory impairments. Conclusions:Peripheral blood biomarkers may interact with pathways related to ApoE4 to predict greater semantic and episodic memory impairments, thus contributing to the pathophysiology of aMCI and AD. Our data suggest that the transition from aMCI to AD could at least in some cases be associated with significant interactions between ApoE4 and those peripheral blood biomarkers.

Keywords: Anion gap, apolipoprotein, biomarkers, dementia, episodic memory, inflammation

DOI: 10.3233/JAD-190114

Journal: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 797-811, 2019