Evaluation of Peripheral Immune Dysregulation in Alzheimer’s Disease and Vascular Dementia

Article type: Research Article

Authors: Guo, Zongjun^{a; 1; *} | Peng, Xing^{b; d; 1} | Li, Hui-Yun^{c; 1} | Wang, Yunlai^b | Qian, Ying^{b; d} | Wang, Zhihong^a | Ye, Dongqing^b | Ji, Xiaoyun^a | Wang, Zhixin^e | Wang, Yanjiang^c | Chen, Dongwan^{c; *} | Lei, Hongxing^{b; d; f; *}

Affiliations: [a] Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, China | [b] CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China | [c] Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China | [d] Cunji Medical School, University of Chinese Academy of Sciences, Beijing, China | [e] Qingdao Chengyang People’s Hospital, Qingdao, China | [f] Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, China

Correspondence: [*] Correspondence to: Hongxing Lei, CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. E-mail: [email protected]. and Zongjun Guo, Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, China. E-mail: [email protected]. and Dongwan Chen, Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China. E-mail: [email protected].

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

Abstract: Immune dysregulation has been observed in the brain and blood of patients with Alzheimer’s disease (AD). However, a convenient assay to evaluate peripheral immune dysregulation in AD has not been developed, partly due to the inconsistent observations from different studies. We hypothesized that peripheral immune dysregulation may only exist in a subpopulation of AD patients; therefore it may be valuable to identify this subpopulation with a convenient assay. Along this line, we selected 14 candidate genes based on our analysis of microarray data on peripheral blood of AD and other diseases. We used RT-qPCR to examine the expression of these 14 genes in a cohort of 288 subjects, including 74 patients with AD, 64 patients with mild cognitive impairment (MCI), 51 patients with vascular dementia (VaD), and 99 elderly controls with no cognitive dysfunction/impairment. Seven of these 14 genes displayed significant difference in group comparison. Switching from group comparison to individualized evaluation revealed more in-depth information. First, there existed a wide dynamic range for the expression of these immune genes in peripheral blood even within the control group. Second, for the vast majority of the patients (AD, VaD, and MCI patients), the expression of these genes fell within the dynamic range of the control group. Third, a small portion of outliers were observed in the patient groups, more so in the VaD group than that in the AD or MCI groups. This is our first attempt to conduct personalized evaluation of peripheral immune dysregulation in AD and VaD. These findings may be applicable to the identification of peripheral immune dysregulation in AD and VaD patients which may lead to tailored treatment toward those patients.

Keywords: Alzheimer’s disease, immune dysregulation, peripheral blood, precision medicine, vascular dementia

DOI: 10.3233/JAD-190666

Journal: Journal of Alzheimer's Disease, vol. 71, no. 4, pp. 1175-1186, 2019