Hippocampal expression of cell-adhesion glycoprotein neuroplastin is altered in Alzheimer's disease.

Katarina Ilic,Natasa Jovanov‐Milosevic,Svjetlana Kalanj‐Bognar,Nenad Bogdanovic,Nikola Habek,Goran Simic,Kristina Mlinac‐Jerkovic

doi:10.1111/jcmm.13998

Katarina Ilic, Natasa Jovanov‐Milosevic + Show 5 more

Open Access

https://doi.org/10.1111/jcmm.13998

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Abstract

Cell‐adhesion glycoprotein neuroplastin (Np) is involved in the regulation of synaptic plasticity and balancing hippocampal excitatory/inhibitory inputs which aids in the process of associative memory formation and learning. Our recent findings show that neuroplastin expression in the adult human hippocampus is specifically associated with major hippocampal excitatory pathways and is related to neuronal calcium regulation. Here, we investigated the hippocampal expression of brain‐specific neuroplastin isoform (Np65), its relationship with amyloid and tau pathology in Alzheimer's disease (AD), and potential involvement of neuroplastin in tissue response during the disease progression. Np65 expression and localization was analysed in six human hippocampi with confirmed AD neuropathology, and six age‐/gender‐matched control hippocampi by imunohistochemistry. In AD cases with shorter disease duration, the Np65 immunoreactivity was significantly increased in the dentate gyrus (DG), Cornu Ammonis 2/3 (CA2/3), and subiculum, with the highest level of Np expression being located on the dendrites of granule cells and subicular pyramidal neurons. Changes in the expression of neuroplastin in AD hippocampal areas seem to be related to the progression of disease. Our study suggests that cell‐adhesion protein neuroplastin is involved in tissue reorganization and is a potential molecular marker of plasticity response in the early neurodegeneration process of AD.

Highlights

Studies in literature have indicated multiple differentphysiological functions of cell‐adhesion molecule (CAM) neuroplastin in the human brain such as: the association of neuroplastin gene polymorphisms with cognitive abilities and cortical thickness in adolescents[1]; single nucleotide polymorphisms that are associated with a higher risk of developing schizophrenia.[2]
We recently reported that immunohistochemical localization of neuroplastin in the adult human hippocampus delineates hippocampal circuitry and its principal excitatory pathways, and that there is a link between Np expression and calcium regulation in murine cortical hippocampal glutamatergic neurons.[3]
We found increased neuroplastin immunoreactivity in all major hippocampal areas (Ammon's horn, dentate gyrus, subiculum) affected by Alzheimer's disease (AD) pathology when compared to age‐/gender‐matched controls

Summary

| INTRODUCTION

Studies in literature have indicated multiple different (patho)physiological functions of cell‐adhesion molecule (CAM) neuroplastin in the human brain such as: the association of neuroplastin gene polymorphisms with cognitive abilities and cortical thickness in adolescents[1]; single nucleotide polymorphisms that are associated with a higher risk of developing schizophrenia.[2] we recently reported that immunohistochemical localization of neuroplastin in the adult human hippocampus delineates hippocampal circuitry and its principal excitatory pathways, and that there is a link between Np expression and calcium regulation in murine cortical hippocampal glutamatergic neurons.[3] Two isoforms of neuroplastin, Np55 and brain‐specific Np65, have been described.[4] Neuroplastin functions in several vital processes in the mammalian central nervous system including neurite outgrowth,[5] regulation of synaptic plasticity,[6] This strongly indicates that CAM neuroplastin is involved in molecular events underlying tissue response in neurodegeneration

| MATERIALS AND METHODS

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Findings

| DISCUSSION