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New Rat Model Could Uncover Important Answers in Alzheimer’s Research

Summary: Researchers have developed a new rat model of Alzheimer’s disease that can be used to study the accumulation of amyloid plaques.

Source: University of Missouri Columbia.

Alzheimer’s disease currently affects more than 5.5 million Americans and is one of the costliest diseases to treat, according to the Alzheimer’s Association. Characterized by a buildup of plaque in the brain, few animal models exist that researchers could use to study this devastating disorder. Now, a team of researchers from the University of Missouri, publishing in PLOS ONE, developed a rat model that can be used to study the buildup of amyloid plaques and vascular abnormalities in the brain.


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

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-β (Aβ) showed extensive and mostly diffuse Aβ 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 Aβ deposits in cortical and leptomeningeal blood vessel walls and venous collagenosis. In addition to the Aβ 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.

Source: Jeff Sossamon – University of Missouri Columbia Publisher: Organized by Image Source: image is credited to Yuksel Agca, MU College of Veterinary Medicine. Original Research: Open access research for “Memory deficiency, cerebral amyloid angiopathy, and amyloid-β plaques in APP+PS1 double transgenic rat model of Alzheimer’s disease” by Diana Klakotskaia, Cansu Agca, Rachel A. Richardson, Edward G. Stopa, Todd R. Schachtman, and Yuksel Agca in PLOS ONE. Published April 11 2018. doi:10.1371/journal.pone.0195469


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