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Impacts of CD33 Genetic Variations on the Atrophy Rates of Hippocampus and Parahippocampal Gyrus in Normal Aging and Mild Cognitive Impairment

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Abstract

The cluster of differentiation 33 (CD33) has been proved as a susceptibility locus associated with late-onset Alzheimer’s disease (LOAD) based on recent genetic studies. Numerous studies have shown that multiple neuroimaging measures are potent predictors of AD risk and progression, and these measures are also affected by genetic variations in AD. Figuring out the association between CD33 genetic variations and AD-related brain atrophy may shed light on the underlying mechanisms of CD33-related AD pathogenesis. Thus, we investigated the influence of CD33 genotypes on AD-related brain atrophy to clarify the possible means by which CD33 impacts AD. A total of 48 individuals with probable AD, 483 mild cognitive impairment, and 281 cognitively normal controls were recruited from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. We investigated the influence of CD33 SNPs on hippocampal volume, parahippocampal gyrus volume, posterior cingulate volume, middle temporal volume, hippocampus CA1 subregion volume, and entorhinal cortex thickness. We found that brain regions significantly affected by CD33 genetic variations were restricted to hippocampal and parahippocampal gyrus in hybrid population, which were further validated in subpopulation (MCI and NC) analysis. These findings reaffirm the importance of the hippocampal and parahippocampal gyrus in AD pathogenesis, and present evidences for the CD33 variations influence on the atrophy of specific AD-related brain structures. Our findings raise the possibility that CD33 polymorphisms contribute to the AD risk by altering the neuronal degeneration of hippocampal and parahippocampal gyrus.

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Acknowledgments

Data collection and sharing was funded by the ADNI (National Institutes of Health U01 AG024904). ADNI is funded by the National Institute on Aging; the National Institute of Biomedical Imaging and Bioengineering; the Alzheimer’s Association; the Alzheimer’s Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Co., F. Hoffmann-LaRoche Ltd and Genetech, Inc.; GE Healthcare; Innogenetics, NV; IXICO Ltd; Janssen Alzheimer Immunotherapy Research & Development LLC; Medpace, Inc; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Novartis Pharmaceuticals, Co., Pfizer, Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Co. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private-sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization was the Northern California Institute for Research and Education, and the study was coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This work was also supported by grants from the National Natural Science Foundation of China (81471309, 81171209, 81371406, 81501103, 81571245), the Shandong Provincial Outstanding Medical Academic Professional Program, Qingdao Key Health Discipline Development Fund, Qingdao Outstanding Health Professional Development Fund, and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders.

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    Authors and Affiliations

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

      Wen-Ying Wang, Ying Liu, Fu-Rong Sun, Meng-Shan Tan, Chen-Chen Tan, Lan Tan & Jin-Tai Yu

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

      Hui-Fu Wang & Lan Tan

    3. College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266000, China

      Lin Tan

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

      Teng Jiang

    5. Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA

      Jin-Tai Yu

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    1. Wen-Ying Wang
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    Alzheimer’s Disease Neuroimaging Initiative

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    Correspondence to Lan Tan or Jin-Tai Yu.

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    The authors declare no conflicts of interest.

    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

    Wen-Ying Wang and Ying Liu contributed equally to this work.

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    Wang, WY., Liu, Y., Wang, HF. et al. Impacts of CD33 Genetic Variations on the Atrophy Rates of Hippocampus and Parahippocampal Gyrus in Normal Aging and Mild Cognitive Impairment. Mol Neurobiol 54, 1111–1118 (2017). https://doi.org/10.1007/s12035-016-9718-4

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    • DOI: https://doi.org/10.1007/s12035-016-9718-4

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