Association of neurogranin gene expression with Alzheimer's disease pathology in the perirhinal cortex

Xiaoyan Sun; Qian Wang; Kaj Blennow; Henrik Zetterberg; Micheline McCarthy; David A Loewenstein; Regina Vontell; Zhenyu Yue; Bin Zhang

doi:10.1002/trc2.12162

Association of neurogranin gene expression with Alzheimer's disease pathology in the perirhinal cortex

Alzheimers Dement (N Y). 2021 Apr 9;7(1):e12162. doi: 10.1002/trc2.12162. eCollection 2021.

Authors

Xiaoyan Sun^{1

2}, Qian Wang^{3

4

5

6}, Kaj Blennow^{7

8}, Henrik Zetterberg^{7

8

9

10}, Micheline McCarthy¹, David A Loewenstein¹¹, Regina Vontell^{1

2}, Zhenyu Yue³, Bin Zhang^{4

5

6}

Affiliations

¹ Department of Neurology University of Miami Miller School of Medicine Miami Florida USA.
² Evelyn F. McKnight Brain Institute Brain Endowment Bank University of Miami Miller School of Medicine Miami Florida USA.
³ Departments of Neurology and Neuroscience Friedman Brain Institute, Icahn School of Medicine at Mount Sinai New York New York USA.
⁴ Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York New York USA.
⁵ Mount Sinai Center for Transformative Disease Modeling Icahn School of Medicine at Mount Sinai New York New York USA.
⁶ Icahn Institute of Genomics and Multi-scale Biology Icahn School of Medicine at Mount Sinai New York New York USA.
⁷ Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy at the University Gothenburg Mölndal Sweden.
⁸ Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden.
⁹ Department of Neurodegenerative Disease UCL Institute of Neurology London UK.
¹⁰ UK Dementia Research Institute at UCL London UK.
¹¹ Department of Psychiatry and Behavioral Sciences Center for Cognitive Neuroscience and Aging University of Miami Miller School of Medicine Miami Florida USA.

Abstract

Introduction: Synaptic damage is a key pathology of Alzheimer's disease (AD). The mechanism underlying synaptic vulnerability in AD remains elusive.

Methods: Using a large-scale transcriptomic dataset, we analyzed the neurogranin-centered integrative gene network and assessed the correlation of neurogranin (NRGN) gene expression with AD pathology in post mortem brains. We studied the association of NRGN expression with Clinical Dementia Rating (CDR) and neuropathological diagnosis of AD.

Results: We find that the genes positively correlated with NRGN expression in AD are involved in synaptic transmission and cation channel pathways. NRGN expression is correlated with amyloid and tau pathology in the perirhinal cortex of post mortem brains. NRGN expression is associated with the diagnosis of AD and correlated with CDR.

Discussion: Transcriptional regulation of the gene encoding for synaptic protein is involved in selective synaptic damage in AD. Identifying the genes associated with synaptic damage pathways in AD may provide targets for intervention.

Keywords: Alzheimer's disease; amyloid; integrative gene network; neurogranin; perirhinal cortex; synapse; tau.

Abstract

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