Identification of molecular alterations in leukocytes from gene expression profiles of peripheral whole blood of Alzheimer's disease

Scientific Reports
Hongdong LiZheng Guo

Abstract

Blood-based test has been considered as a promising way to diagnose and study Alzheimer's disease (AD). However, the changed proportions of the leukocytes under disease states could confound the aberrant expression signals observed in mixed-cell blood samples. We have previously proposed a method, Ref-REO, to detect the leukocyte specific expression alterations from mixed-cell blood samples. In this study, by applying Ref-REO, we detect 42 and 45 differentially expressed genes (DEGs) between AD and normal peripheral whole blood (PWB) samples in two datasets, respectively. These DEGs are mainly associated with AD-associated functions such as Wnt signaling pathways and mitochondrion dysfunctions. They are also reproducible in AD brain tissue, and tend to interact with the reported AD-associated biomarkers and overlap with targets of AD-associated PWB miRNAs. Moreover, they are closely associated with aging and have severer expression alterations in the younger adults with AD. Finally, diagnostic signatures are constructed from these leukocyte specific alterations, whose area under the curve (AUC) for predicting AD is higher than 0.73 in the two AD PWB datasets. In conclusion, gene expression alterations in leukocytes could be ext...Continue Reading

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Citations

Apr 10, 2019·Immunological Investigations·Humera InayatAkhter Ali Baloch
Mar 25, 2020·Aging·Jack KellyXinzhong Li
Feb 28, 2020·Scientific Reports·Taesic Lee, Hyunju Lee
Sep 4, 2020·Journal of Neurochemistry·Marah C RuntschStefano Angiari

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Datasets Mentioned

BETA
GSE28491

Methods Mentioned

BETA
flow cytometry

Software Mentioned

REO
Ref

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