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Regional astrocyte dysregulation and altered glymphatic-related markers in Alzheimer's disease frontal cortex
Harry Alexopoulos1, Xanthippi P Louka1, Edoardo Rosario De Natale2
1Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
Introduction:
Astrocyte dysfunction is central to Alzheimer's disease (AD), yet expression patterns of astrocytic markers remain poorly defined. We measured Aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) in post-mortem frontal cortex of AD patients and controls across BrainNet Europe (BNE) stages.
Methods:
We assessed marker expression across gray and white matter with immunohistochemistry and immunofluorescence.
Results:
In AD, gray-matter AQP4 area-fraction did not differ significantly overall by immunohistochemistry, while a stage-dependent increase emerged by BNE VI in both gray and white matter. AQP4/amyloid-β (Aβ) and AQP4/tau ratios were significantly reduced, consistent with reduced AQP4 retention relative to local proteinopathy burden. GFAP intensity was significantly decreased in both gray and white matter of AD patients, with disorganized peri-plaque morphology in gray matter.
Discussion:
These findings reveal compartment- and stage-specific astrocytic dysregulation in AD frontal cortex and identify local loss of AQP4 around proteinopathy. They support investigation of astrocyte/glymphatic-related pathways as biomarkers and therapeutic targets.
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