protein
Aquaporin-4
aka AQP-4
Gene
AQP4
Organism
Homo sapiens(9606)
Length
323 aa
Mass
34,830 Da
Aquaporin-4 (AQP4) is a water channel protein that forms water-specific channels essential for brain water homeostasis (UniProt: P55087). It plays a critical role in the glymphatic system, facilitating water exchange across the blood-brain barrier and enabling clearance of solutes, including soluble beta-amyloid peptides, from brain interstitial fluid through paravascular and paravenous drainage pathways.
AQP4 is predominantly expressed in astrocytes and ependymal cells, where it regulates cerebrospinal fluid dynamics and interstitial fluid clearance. Mutations in AQP4 cause megalencephalic leukoencephalopathy with subcortical cysts 4 (MLC4), an autosomal recessive disorder characterized by macrocephaly, developmental delay, and seizures. The protein's role in amyloid-beta clearance suggests broader relevance to neurological pathology.
In Alzheimer's disease, AQP4 is upregulated in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of 1.476 across two subcellular fractions (Chaparral AD proteomics). This elevation may reflect compensatory upregulation of the glymphatic system in response to impaired amyloid clearance and neuroinflammation characteristic of AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
+2.168
S3
+0.784
Mean log₂FC across detected fractions: +1.476 (2 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Forms a water-specific channel (PubMed:19383790, PubMed:7559426, PubMed:8601457). Plays an important role in brain water homeostasis (PubMed:37143309). It is involved in glymphatic solute transport and is required for a normal rate of water exchange across the blood brain interface. Required for normal levels of cerebrospinal fluid influx into the brain cortex and parenchyma along paravascular spaces that surround penetrating arteries, and for normal drainage of interstitial fluid along paravenous drainage pathways. Thereby, it is required for normal clearance of solutes from the brain interstitial fluid, including soluble beta-amyloid peptides derived from APP. Plays a redundant role in urinary water homeostasis and urinary concentrating ability (By similarity)
Disease associations
Megalencephalic leukoencephalopathy with subcortical cysts 4, remittingMLC4
An autosomal recessive disorder characterized by macrocephaly apparent in infancy, developmental delay, delayed walking, variable cognitive decline, behavioral abnormalities, and early-onset seizures. Brain imaging shows swelling of the cerebral white matter and subcortical cysts in the anterior temporal region. The severity of neurologic dysfunction and brain abnormalities tends to improve with time, indicating a remitting disease course.
Sources
Last updated 5/8/2026, 6:30:54 AM