Abstract
Astrocytes play a major role in the pathogenesis of a range of neurodegenerative diseases, including Alzheimer’s disease (AD), undergoing dramatic morphological and molecular changes that can cause potentially both beneficial and detrimental effects. They comprise a heterogeneous population, requiring a panel of specific phenotype markers to identify astrocyte subtypes, changes in function and their relation to pathology. This study aimed to characterise expression of the astrocyte marker N-myc downstream regulated gene 2 (NDRG2) in the ageing brain, investigate the relationship between NDRG2 and a panel of astrocyte markers, and relate NDRG2 expression to pathology. NDRG2 specifically immunolabelled the cell body and radiating processes of astrocytes in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) neuropathology cohort. Expression of NDRG2 did not correlate with other astrocyte markers, including glial fibrillary acidic protein (GFAP), excitatory amino acid transporter 2 (EAAT2) and glutamine synthetase (GS). NDRG2 showed a relationship to AT8+ neurofibrillary tangles (p = 0.001) and CD68+ microglia (p = 0.047), but not β-amyloid plaques or astrocyte nuclear γH2AX immunoreactivity, a marker of DNA damage response. These findings provide new insight into the astrocyte response to pathology in the ageing brain, and suggest NDRG2 may be a potential target to modulate this response.
Highlights
While much of the focus in dementia research has been on the neuron, other cell types are important
Quantitative assessment of the immunoreactive profile of N-myc downstream regulated gene 2 (NDRG2), glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and excitatory amino acid transporter 2 (EAAT2) across the cohort is shown in Table 1 and Figure 3A
As astrocytes respond to pathology in their immediate vicinity, we investigated the relationship of NDRG2 to local measures of Alzheimer’s disease (AD) pathology, assessed by Aβ and AT8+% area immunoreactivity
Summary
While much of the focus in dementia research has been on the neuron, other cell types are important. Astrocytes, the most abundant cell type in the central nervous system (CNS), play an essential role in homeostasis, including neuronal support, synapse formation and function, maintenance and metabolism [1,2]. They are classified into two major groups on the basis of their morphology and anatomical location; the fibrous astrocytes of the white matter and the protoplasmic astrocytes of the grey matter [2]. As part of the tripartite synapse, astrocytes regulate levels of neurotransmitters, including the excitatory transmitter glutamate, and play a major role in preventing excitotoxicity caused by the accumulation of excess glutamate [6,7]. In addition to regulating neurotransmission, astrocytes are responsible for providing metabolic support to neurons via the lactate shuttle [9]
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