Research Papers: Gerotarget (Focus on Aging):

Effect of HMGCR genetic variation on neuroimaging biomarkers in healthy, mild cognitive impairment and Alzheimer’s disease cohorts

Lei Cao, Hui-Fu Wang, Lin Tan _, Fu-Rong Sun, Meng-Shan Tan, Chen-Chen Tan, Teng Jiang, Jin-Tai Yu, Lan Tan and Alzheimer’s Disease Neuroimaging Initiative

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Oncotarget. 2016; 7:13319-13327. https://doi.org/10.18632/oncotarget.7797

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Lei Cao1,*, Hui-Fu Wang1,*, Lin Tan2, Fu-Rong Sun3, Meng-Shan Tan3, Chen-Chen Tan3, Teng Jiang4, Jin-Tai Yu1, Lan Tan1,2,3 and Alzheimer’s Disease Neuroimaging Initiative

1 Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China

2 College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China

3 Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

4 Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China

* These authors have contributed equally to this work

Correspondence to:

Lan Tan, email:

Jin-Tai Yu, email:

Keywords: Alzheimer’s disease, brain structure, HMGCR, neuroimaging, glucose metabolism, Gerotarget

Received: November 25, 2015 Accepted: February 11, 2016 Published: February 29, 2016


Alzheimer’s disease (AD) has become a considerable public health issue. The mechanisms underlying AD onset and progression remain largely unclear. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is a strong functional AD candidate gene because it encodes part of the statin-binding domain of the enzyme, which serves as the rate-limiting step in cholesterol synthesis in all mammalian cells. Here, we evaluated the potential role of HMGCR (rs3846662) in AD-related pathology by assessing neuroimaging biomarkers. We enrolled in 812 subjects from the Alzheimer’s disease Neuroimaging Initiative dataset. In general, it is possible that HMGCR (rs3846662) could be involved in preventing the atrophy of right entorhinal (P=0.03385) and left hippocampus (P=0.01839) in the follow-up research of two years. What’s more, it lowered the drop rate of glucose metabolism in right temporal. We then further validated them in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. All the results in the MCI groups confirmed the association. The results of our study indicated that HMGCR (rs3846662) plays a vital role in AD pathology mainly by influencing brain structure and glucose metabolism during AD progression.

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