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Impact of Common Variations in PLD3 on Neuroimaging Phenotypes in Non-demented Elders

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Abstract

Rare variants of phospholipase D3 (PLD3) have been identified as Alzheimer’s disease (AD) susceptibility loci, whereas little is known about the potential role of common variants in the progression of AD. To examine the impact of genetic variations in PLD3 on neuroimaging phenotypes in a large non-demented population. A total of 261 normal cognition (NC) and 456 mild cognitive impairment (MCI) individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database are included in our analysis. Multiple linear regression models were applied to examine the association between four single-nucleotide polymorphisms (SNPs; rs7249146, rs4490097, rs12151243, and rs10407447) with the florbetapir retention on florbetapir 18F amyloid positron emission tomography (AV45-PET), the cerebral metabolic rate for glucose (CMRgl) on 18F-fluorodeoxyglucose PET (FDG-PET), and regional volume on magnetic resonance imaging (MRI) at baseline and in the cohort study. We did not detect any significant associations of PLD3 SNPs with florbetapir retention on AV45-PET. In the analysis of FDG-PET, rs10407447 was associated with the CMRgl in the left angular gyrus and bilateral posterior cingulate cortex in the MCI group. Regarding the MRI analysis, rs10407447 was also associated with bilateral inferior lateral ventricle and lateral ventricle volume in MCI group. The main findings of our study provide evidence that support the possible role of PLD3 common variants in influencing AD-related neuroimaging phenotypes. Nevertheless, further work is necessary to explain the functional mechanisms of differences and confirm the causal variants.

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Acknowledgments

Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). This research was also supported by National Natural Science Foundation of China (81171209, 81371406, 81000544), the Shandong Provincial Outstanding Medical Academic Professional Program, and the Qingdao Key Health Discipline Development Fund.

Conflict of interest

The authors declare that they have no competing interests

Author information

Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, 266071, Shandong, China

    Chong Wang, Meng-Shan Tan, Ying Liu, Lan Tan & Jin-Tai Yu

  2. Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China

    Chong Wang

  3. Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China

    Hui-Fu Wang & Lan Tan

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

    Teng Jiang

  5. Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China

    Dao-Qiang Zhang

  6. Memory and Aging Center, Department of Neurology, University of California, 675 Nelson Rising Lane, Suite 190, Box 1207, San Francisco, CA, 94158, USA

    Jin-Tai Yu

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  1. Chong Wang
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Alzheimer’s Disease Neuroimaging Initiative

Corresponding authors

Correspondence to Lan Tan or Jin-Tai Yu.

Additional information

Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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Wang, C., Wang, HF., Tan, MS. et al. Impact of Common Variations in PLD3 on Neuroimaging Phenotypes in Non-demented Elders. Mol Neurobiol 53, 4343–4351 (2016). https://doi.org/10.1007/s12035-015-9370-4

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  • DOI: https://doi.org/10.1007/s12035-015-9370-4

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