Memory deficiency, cerebral amyloid angiopathy, and amyloid-beta plaques in APP+PS1 double transgenic rat model of Alzheimer's disease

作者：Klakotskaia Diana; Agca Cansu; Richardson Rachel A; Stopa Edward G; Schachtman Todd R; Agca Yuksel^*

来源：PLos One, 2018, 13(4): e0195469.

DOI：10.1371/journal.pone.0195469

Transgenic rat models of Alzheimer's disease were used to examine differences in memory and brain histology. Double transgenic female rats (APP+PS1) over-expressing human amyloid precursor protein (APP) and presenilin 1 (PS1) and single transgenic rats (APP21) over-expressing human APP were compared with wild type Fischer rats (WT). The Barnes maze assessed learning and memory and showed that both APP21 and APP+PS1 rats made significantly more errors than the WT rats during the acquisition phase, signifying slower learning. Additionally, the APP+PS1 rats made significantly more errors following a retention interval, indicating impaired memory compared to both the APP21 and WT rats. Immunohistochemistry using an antibody against amyloid-beta (A beta) showed extensive and mostly diffuse A beta plaques in the hippocampus and dense plaques that contained tau in the cortex of the brains of the APP+PS1 rats. Furthermore, the APP+PS1 rats also showed vascular changes, including cerebral amyloid angiopathy with extensive A beta deposits in cortical and leptomeningeal blood vessel walls and venous collagenosis. In addition to the A beta accumulation observed in arterial, venous, and capillary walls, APP+PS1 rats also displayed enlarged blood vessels and perivascular space. Overall, the brain histopathology and behavioral assessment showed that the APP+PS1 rats demonstrated behavioral characteristics and vascular changes similar to those commonly observed in patients with Alzheimer's disease.

• 出版日期2018-4-11