Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the elderly, and is featured by abnormal aggregation of plaques and tangles in brain, progressive memory loss and cognitive impairment.

Age is the most important risk factor for AD. The incidence increases exponentially with age and doubles every five years after age 65. Besides, genetic factor is another crucial risk factor. It is reported that over 80% of genetic risk loci identified by genome wide association studies (GWASs) are located in non-coding regions of the genome. These loci are likely to contribute to AD by altering gene expression.

Therefore, a complete characterization of the transcriptomic alterations and the regulatory mechanisms that underpin AD may provide essential evidence to fill the gap between genetic variations and AD development.

Recently, the research group led by Prof. YAO Yonggang at Kunming Institute of Zoology of Chinese Academy of Sciences identified several upstream regulator genes which may play a crucial role in regulatory network of gene expression in AD brain by a systematic integrative analysis based on the largest collection of brain expression profiles of AD and other AD related omics data.

Published in Alzheimer’s & Dementia, this study suggested that targeting the expression of these upstream regulators in early stage of the disease may reverse the disease progression.

Using a convergent functional genomic method, the researchers performed an integrative analysis of available high-throughput brain expression profiling datasets from AD patients and controls. They provided a complete and robust list of differential expressed genes (DEGs) in AD brain, and identified several candidate upstream regulators in the gene expression network, such as YAP1.

Functional experiments of YAP1 have suggested that expression perturbations of upstream regulator genes at the early stage of AD development might be damaging, by affecting expression of downstream genes and further promoting AD progression. Candidate upstream regulators found in this study might act as potential therapeutic targets for the treatment of AD.

To promote public sharing of AD-related data, they constructed a webserver AlzData (http://www.AlzData.org) for easy access to their results and other high throughput data.

This study was supported by the Key Program of National Natural Science Foundation of China, the Bureau of Frontier Sciences and Education, the Strategic Priority Research Program (B), and the West Light Foundation of the Chinese Academy of Sciences.