The advantages and disadvantages of AQP4 neural tissue deficiency under pathological conditions, such as inflammation, and relationship with neural diseases, such as Alzheimer's disease, have been previously reported.
Emerging data suggest that AQP4 may also be implicated in the glymphatic system and may be involved in the clearance of beta-amyloid in Alzheimer's disease (AD).
This clinically relevant tool may be crucial to better understand the role of AQP4 in water transport across the BBI, as well as clearance of proteins in neurodegenerative conditions such as Alzheimer's disease.
Altered AQP4 expression is also evident in brain tissue from patients with Alzheimer's disease or normal pressure hydrocephalus; glymphatic MRI scans of patients with normal pressure hydrocephalus show reduced CSF tracer entry and clearance.WHERE NEXT?
Impairment of glymphatic function in the aging rodent brain is associated with reduced perivascular AQP4 localization, and in human subjects, reduced perivascular AQP4 localization is associated with AD diagnosis and pathology.
In addition, we found increased global AQP4 expression of the AD group over both control and mixed dementia groups and a qualitative reduction in perivascular localization of AQP4 in the AD group.
There were two different patterns of GLT-1 and AQP4 expression in the AD group: (i) uneven GLT-1 expression in the neuropil where diffuse but intense AQP4 expression was evident, and (ii) senile plaque-like co-expression of GLT-1 and AQP4.
Based on this, we hypothesized that AQP4-mediated glymphatic system clearance function is a determining factor for time-sensitive treatment of aerobic exercise in patients with AD.
Expression of AQP4 was analyzed in postmortem frontal cortex of cognitively healthy and histopathologically confirmed individuals with AD by Western blot or immunofluorescence for AQP4, amyloid-β 1-42, and glial fibrillary acidic protein.
AQP4, the predominant water channel in the CNS, is involved both in the astrocyte swelling of cytotoxic edema and the resolution of vasogenic edema, and is of pivotal importance in the pathology of brain disorders such as neuromyelitis optica , brain tumors and Alzheimer's disease.
The astrocytic water channel proteins aquaporin 1 (AQP1) and aquaporin 4 (AQP4) are known to be altered in brains affected by several neurodegenerative disorders, including Alzheimer's disease.
These results provide the first evidence that variations in the <i>AQP4</i> gene, whose gene product AQP4 is vital for glymphatic pathway function, may modulate the progression of cognitive decline in AD.
However, making crucial efforts to develop specific agents or drugs that target AQP4 function and test their therapeutic efficiency will be a breakthrough for addressing AD in that AQP4 controls the various physiological as well as pathophysiological features of astrocytes.
This work indicates that a glymphatic pathway that critically relies on astrocytic aquaporin 4, is able to flush solutes from the brain and that deficits in this pathway may contribute to Alzheimer's disease.
The present study examines, by gel electrophoresis and Western blotting, the expression levels of the water channels aquaporin 1 (AQP1) and aquaporin 4 (AQP4) in the frontal cortex (area 8) homogenates of sporadic CJD cases (six men, four women; seven cases with methionine/methionine at codon 129 and PrP type 1; two cases with valine/valine at codon 129 and PrP type 2, and one case methionine/valine at codon 129 and PrP type 1) compared with age-matched controls, and cases with Alzheimer's disease (AD, stage VI of Braak and Braak) and diffuse Lewy body disease (DLB).