Astrocytic proteins involved in regulation of the extracellular environment are increased in the Alzheimer's disease middle temporal gyrus
Alzheimer's disease (AD) has complex pathophysiology involving numerous cell types and brain processes. Astrocyte involvement in AD is gaining increased attention, however a complete characterisation of astrocytic changes in the AD human brain is warranted. Astrocytes perform important homeosta...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996124003516 |
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| author | Henry Liu Adelie Y.S. Tan Nasim F. Mehrabi Clinton P. Turner Maurice A. Curtis Richard L.M. Faull Mike Dragunow Malvindar K. Singh-Bains Amy M. Smith |
| author_facet | Henry Liu Adelie Y.S. Tan Nasim F. Mehrabi Clinton P. Turner Maurice A. Curtis Richard L.M. Faull Mike Dragunow Malvindar K. Singh-Bains Amy M. Smith |
| author_sort | Henry Liu |
| collection | DOAJ |
| description | Alzheimer's disease (AD) has complex pathophysiology involving numerous cell types and brain processes. Astrocyte involvement in AD is gaining increased attention, however a complete characterisation of astrocytic changes in the AD human brain is warranted. Astrocytes perform important homeostatic functions including regulation of the extracellular microenvironment, critical for the health of all brain cells. We have investigated changes to key astrocyte proteins involved in the regulation of CNS extracellular environment in the human AD middle temporal gyrus (MTG): aquaporin-4 (AQP-4), glutamate transporter-1 (GLT-1) and inwardly-rectifying potassium channel 4.1 (Kir4.1). We have used a high-throughput human brain tissue microarray platform with automated quantitative image analysis to measure protein changes in a large cohort of neurological control and AD cases. We found increased astrocytic glial acidic fibrillary protein (GFAP), AQP-4, GLT-1 and Kir4.1 expression that correlates with advancing Braak stage, increasing amyloid pathology and, to a greater extent, the degree of tau pathology. We confirmed that Kir4.1 immunostaining is predominantly found in astrocytes and revealed a novel redistribution of Kir4.1 protein expression into astrocytic processes in the AD MTG. Our study presents novel and potentially modifiable glial changes in the AD human brain that are critical to our understanding of disease pathogenesis. |
| format | Article |
| id | doaj-art-2d117239cff24b55ad18c2e4f29d2f10 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-2d117239cff24b55ad18c2e4f29d2f102025-01-07T04:17:05ZengElsevierNeurobiology of Disease1095-953X2025-01-01204106749Astrocytic proteins involved in regulation of the extracellular environment are increased in the Alzheimer's disease middle temporal gyrusHenry Liu0Adelie Y.S. Tan1Nasim F. Mehrabi2Clinton P. Turner3Maurice A. Curtis4Richard L.M. Faull5Mike Dragunow6Malvindar K. Singh-Bains7Amy M. Smith8Centre for Brain Research and Department of Pharmacology and Clinical Pharmacology, University of Auckland, New ZealandCentre for Brain Research and Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New ZealandCentre for Brain Research and Department of Pharmacology and Clinical Pharmacology, University of Auckland, New ZealandDepartment of Anatomical Pathology, Pathology and Laboratory Medicine, Auckland City Hospital, Auckland, New ZealandCentre for Brain Research and Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New ZealandCentre for Brain Research and Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New ZealandCentre for Brain Research and Department of Pharmacology and Clinical Pharmacology, University of Auckland, New ZealandCentre for Brain Research and Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New ZealandCentre for Brain Research and Department of Pharmacology and Clinical Pharmacology, University of Auckland, New Zealand; Corresponding author.Alzheimer's disease (AD) has complex pathophysiology involving numerous cell types and brain processes. Astrocyte involvement in AD is gaining increased attention, however a complete characterisation of astrocytic changes in the AD human brain is warranted. Astrocytes perform important homeostatic functions including regulation of the extracellular microenvironment, critical for the health of all brain cells. We have investigated changes to key astrocyte proteins involved in the regulation of CNS extracellular environment in the human AD middle temporal gyrus (MTG): aquaporin-4 (AQP-4), glutamate transporter-1 (GLT-1) and inwardly-rectifying potassium channel 4.1 (Kir4.1). We have used a high-throughput human brain tissue microarray platform with automated quantitative image analysis to measure protein changes in a large cohort of neurological control and AD cases. We found increased astrocytic glial acidic fibrillary protein (GFAP), AQP-4, GLT-1 and Kir4.1 expression that correlates with advancing Braak stage, increasing amyloid pathology and, to a greater extent, the degree of tau pathology. We confirmed that Kir4.1 immunostaining is predominantly found in astrocytes and revealed a novel redistribution of Kir4.1 protein expression into astrocytic processes in the AD MTG. Our study presents novel and potentially modifiable glial changes in the AD human brain that are critical to our understanding of disease pathogenesis.http://www.sciencedirect.com/science/article/pii/S0969996124003516Alzheimer's diseaseAstrocytesTissue microarrayInwardly rectifying potassium channel 4.1 (Kir4.1) |
| spellingShingle | Henry Liu Adelie Y.S. Tan Nasim F. Mehrabi Clinton P. Turner Maurice A. Curtis Richard L.M. Faull Mike Dragunow Malvindar K. Singh-Bains Amy M. Smith Astrocytic proteins involved in regulation of the extracellular environment are increased in the Alzheimer's disease middle temporal gyrus Neurobiology of Disease Alzheimer's disease Astrocytes Tissue microarray Inwardly rectifying potassium channel 4.1 (Kir4.1) |
| title | Astrocytic proteins involved in regulation of the extracellular environment are increased in the Alzheimer's disease middle temporal gyrus |
| title_full | Astrocytic proteins involved in regulation of the extracellular environment are increased in the Alzheimer's disease middle temporal gyrus |
| title_fullStr | Astrocytic proteins involved in regulation of the extracellular environment are increased in the Alzheimer's disease middle temporal gyrus |
| title_full_unstemmed | Astrocytic proteins involved in regulation of the extracellular environment are increased in the Alzheimer's disease middle temporal gyrus |
| title_short | Astrocytic proteins involved in regulation of the extracellular environment are increased in the Alzheimer's disease middle temporal gyrus |
| title_sort | astrocytic proteins involved in regulation of the extracellular environment are increased in the alzheimer s disease middle temporal gyrus |
| topic | Alzheimer's disease Astrocytes Tissue microarray Inwardly rectifying potassium channel 4.1 (Kir4.1) |
| url | http://www.sciencedirect.com/science/article/pii/S0969996124003516 |
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