- AQP4 expression is highly organised, peaking in subcortical, ventral and periventricular territories consistent with a clearance axis near CSF reservoirs.
- AQP4-enriched regions exhibit lower normative blood perfusion and spatial proximity to areas commonly affected by cerebral small vessel disease.
- AQP4 colocalises with atrophy in tau and TDP-43 proteinopathies, aligns with neuroinflammation PET markers and associates with higher glioma frequency.
Sci Adv. 2026 Sep 25;12(39):eaeg8117. doi: 10.1126/sciadv.aeg8117. Epub 2026 Sep 23.
ABSTRACT
Aquaporin-4 (AQP4) water channels support the glymphatic system, a brain-wide pathway that clears cerebral waste products. Here, we use AQP4 gene expression to reconstruct a whole-brain glymphatic-related topography and link it to vascular physiology, glioma, and vulnerability to neurodegenerative diseases. We find that AQP4 expression is highly organized across the brain, peaking in subcortical, ventral, and periventricular territories, consistent with a clearance axis near cerebrospinal fluid reservoirs and perivascular interfaces. Linking AQP4 expression to vascular organization, AQP4-enriched regions show lower normative blood perfusion, but lie close to areas commonly affected by cerebral small vessel disease. Turning to neurodegeneration, we find that atrophy patterns colocalize with AQP4 expression, most strongly for tau and TDP-43 proteinopathies, and high-atrophy regions lie close to AQP4 hotspots in anatomical and structural connectome space. Normative positron emission tomography markers of neuroinflammation strengthen the spatial alignment between AQP4 expression and disease atrophy. Last, we show that glioma is most frequent in AQP4-enriched regions. Collectively, this work highlights how AQP4 expression relates to brain physiology and vulnerability.
PMID:42777040 | DOI:10.1126/sciadv.aeg8117
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