Aquaporin‐4 expression is altered around the lateral ventricle in correlation with beta‐amyloid plaque expression in a transgenic mouse model of Alzheimer‘s Disease

Abstract

Accumulation of beta amyloid (Aβ) is central to the pathogenesis of Alzheimer‘s Disease. Aquaporin 4 (AQP4) is a water channel protein expressed in the ependymal lining of the ventricular surface. We hypothesized that time‐dependent AQP4 expression would be altered in the lateral ventricle and cortex of a transgenic mouse model which expresses human amyloid precursor protein, corresponding with Alzheimer‘s Disease progression. Human Aβ expression was examined by immunohistochemistry in four brain quadrants in Tg2576 mice at 3, 8, 12, and 16 months. The average number of Aβ plaques, area per plaque, and percent of brain area covered by plaques significantly increased by 16 months. Lateral ventricles were enlarged in 12 and 16 month Tg2576 mice, concomitant with basal cell hyperplasia around the ventricles. AQP4 expression was observed on the apical and basolateral surfaces of basal cells surrounding the ventricles in 12 and 16 month mice, whereas AQP4 subcellular staining was restricted to the basolateral surface of basal cells at earlier time points and in controls. The altered pattern and distribution of AQP4 expression coincident with an increased number and area of plaques may be indicative of a change in fluid dynamics in later Alzheimer‘s Disease. This research was funded by an APS Summer Undergraduate Research Fellowship and by the University of Dayton Honors and Scholars Program.