Abstract
BackgroundNeuron Glial 2 (NG2) cells are glial cells known to serve as oligodendrocyte progenitors as well as modulators of the neuronal network. Altered NG2 cell morphology and up-regulation as well as increased shedding of the proteoglycan NG2 expressed on the cell surface have been described in rodent models of brain injury. Here we describe alterations in the human NG2 cell population in response to pathological changes characteristic of Alzheimer’s disease (AD).ResultsImmunohistological stainings of postmortem brain specimens from clinically diagnosed and postmortem verified AD patients and non-demented controls revealed reduced NG2 immunoreactivity as well as large numbers of NG2 positive astrocytes in individuals with high amyloid beta plaque load. Since fibrillar amyloid beta (Aβ)1-42 is the major component of AD-related senile plaques, we exposed human NG2 cells to oligomer- and fibril enriched preparations of Aβ1-42. We found that both oligomeric and fibrillar Aβ1-42 induced changes in NG2 cell morphology. Further, in vitro exposure to fibrillar Aβ1-42 decreased the NG2 concentrations in both cell lysates and supernatants. Interestingly, we also found significantly decreased levels of soluble NG2 in the cerebrospinal fluid (CSF) from clinically diagnosed AD patients compared to non-demented individuals. Additionally, the CSF NG2 levels were found to significantly correlate with the core AD biomarkers Aß1-42, T-tau and P-tau.ConclusionOur results demonstrate major alterations in the NG2 cell population in relation to AD pathology which highlights the NG2 cell population as a new attractive research target in the search for cellular mechanisms associated with AD pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/2051-5960-1-7) contains supplementary material, which is available to authorized users.
Highlights
Neuron Glial 2 (NG2) cells are glial cells known to serve as oligodendrocyte progenitors as well as modulators of the neuronal network
Microglial clustering adjacent to plaques, glial nest formation as well as changes in microglial morphology were observed to a higher extent in individuals with high Amyloid beta (Aβ) plaque load (Table 2)
Since decreased levels of Aβ1-42 in cerebrospinal fluid (CSF) have been shown to correlate with increased Aβ load in the brain [55], we suggest that the positive correlation implies an association between lower Aβ1-42 plaque load and higher NG2 levels, and vice versa, further supporting the hypothesis that Aβ affects the amount of soluble NG2
Summary
Neuron Glial 2 (NG2) cells are glial cells known to serve as oligodendrocyte progenitors as well as modulators of the neuronal network. Altered NG2 cell morphology and up-regulation as well as increased shedding of the proteoglycan NG2 expressed on the cell surface have been described in rodent models of brain injury. In addition to the three major glial cell types in the brain i.e. astrocytes, microglia and oligodendrocytes, a fourth glial cell type, called the NG2 cell, has been shown to exist. This glial cell is recognized by its stellate morphology and expression of a specific chondroitin sulphate proteoglycan. The chondroitin sulphate proteoglycan NG2 (and its homologue MSPC in humans) expressed on the NG2 cell surface is a type I transmembrane protein with a core glycoprotein of approximately 300 kDa [1]. The NG2 proteoglycan is found on NG2 cells, and on infiltrating macrophages and on pericytes [9,10,11,12]
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