Regional differences in astrocytic Aquaporin-4 protein levels and distribution in aging and Alzheimer's disease in down syndrome
Year: 2025
Type: article
Study design: Observational Study
Abstract: Aquaporin-4 (AQP4) is implicated in Alzheimer's disease (AD) pathology through its role in astrocytic function, cerebrovascular integrity, and beta-amyloid (Aβ) clearance. Impaired Aβ clearance in AD is linked to changes in AQP4 distribution; however, the role of AQP4 in AD associated with Down Syndrome (DS) is poorly understood. This study investigates AQP4 protein levels, its relationship with Aβ deposition, and distribution patterns in DS. Using human post-mortem brain sections from the frontal and occipital cortex, we analyzed AQP4 and Aβ levels in samples from neurotypical controls, DS, DS with AD (DSAD), and late onset AD (LOAD). Protein levels and distribution were assessed using immunohistochemistry and immunofluorescence with quantitative imaging tools. AQP4 protein levels were higher with age in both neurotypical control and DS groups, but not in the LOAD group. AQP4 and Aβ were positively correlated with age in the frontal cortex of all groups. AQP4 and Aβ were positively correlated with each other after adjusting for age in the frontal cortex in both the control and DS groups which was not observed in the occipital cortex. In the frontal cortex of both DS and DSAD, AQP4 was more frequently distributed to the soma and proximal branches and less to astrocytic endfeet compared to the control group, consistent with previous reports of impaired glymphatic clearance and perivascular regulation. These findings support a relationship between altered AQP4 protein levels and distribution, Aβ accumulation, and region-specific vulnerability in DS and AD.
Source: Neurobiology of Disease
Authors: Cherie A. Stringer, Haley K.S. Miyasato, Kevin A. Camey, Krina A. Ghadia, Elizabeth J. Andrews, Phong T. Ngo, Jesse R. Pascual, Sierra T. Wright, Justine A. Silva, Brianna M. Gawronski, Lourdes Gonzalez, Kevin A. Wood, Michael J. Phelan, Florence Lai, Frederick A. Schmitt, Jordan P. Harp, Adam M. Brickman, Patrick J. Lao, Mark E. Mapstone, Julia K. Kofler, Milos D. Ikonomovic, Elizabeth Head
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,180
Funders: National Institutes of Health, Intellectual and Developmental Disabilities Research Center, NIHR Cambridge Biomedical Research Centre, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1017046091, G1133076894, G115506582, G117713310, G1257541548, G1458362881, G1602633198, G1859882300, G2367657529, Waisman Intellectual and Developmental Disabilities Research Center, G2824222223, G2921403101, G2946245170, Institute for Clinical and Translational Science, UCLA Alzheimer's Disease Research Center, Neurodegeneration in Aging Down Syndrome (NiAD): A Longitudinal Study of Cognition and Biomarkers of Alzheimer's Disease, G40706755, Aging and Dementia in Down Syndrome: Connectivity, Inflammation, and Cerebrovascular Contributions, WASHINGTON UNIVERSITY INTELLECTUAL AND DEVELOPMENTAL DISABILITIES RESEARCH CENTER, G5459524459, G6934007932, University of Pittsburgh Clinical and Translational Science Institute, University of Wisconsin Institute for Clinical and Translational Research, Waisman Center Intellectual and Developmental Disabilities Research Center, Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS), Wisconsin Alzheimer's Disease Research Center, National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), Massachusetts Alzheimer's Disease Research Center (MADRC), The Alzheimer's Disease Research Center at the University of California, Irvine
OpenAlex ID: W4414440461