Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer's disease. (5th February 2015)

• Record Type: Journal Article
• Authors: Kanamaru, Takuya; Kamimura, Naomi; Yokota, Takashi; Iuchi, Katsuya; Nishimaki, Kiyomi; Takami, Shinya; Akashiba, Hiroki; Shitaka, Yoshitsugu; Katsura, Ken-ichiro; Kimura, Kazumi; Ohta, Shigeo
• Is Part Of: Neuroscience letters. Volume 587(2015)
• Page Start: 126
• Page End: 131
• Publication Date: 2015-02-05
• Subjects: Alzheimer's disease -- Amyloid β -- APP transgenic mice -- DAL mice -- Oxidative stress; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2014.12.033
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: We have established a novel mouse model of Alzheimer's disease (the APP/DAL mouse). Pathological changes and memory impairment are accelerated in the APP/DAL mouse. The APP/DAL mouse is useful for examining the role of oxidative stress in the progression and pathogenesis of Alzheimer's disease. Abstract: Oxidative stress is known to play a prominent role in the onset and early stage progression of Alzheimer's disease (AD). For example, protein oxidation and lipid peroxidation levels are increased in patients with mild cognitive impairment. Here, we created a double-transgenic mouse model of AD to explore the pathological and behavioral effects of oxidative stress. Double transgenic (APP/DAL) mice were constructed by crossing Tg2576 (APP) mice, which express a mutant form of human amyloid precursor protein (APP), with DAL mice expressing a dominant-negative mutant of mitochondrial aldehyde dehydrogenase 2 (ALDH2), in which oxidative stress is enhanced. Y-maze and object recognition tests were performed at 3 and 6 months of age to evaluate learning and memory. The accumulation of amyloid plaques, deposition of phosphorylated-tau protein, and number of astrocytes in the brain were assessed histopathologically at 3, 6, 9, and 12–15 months of age. The life span of APP/DAL mice was significantly shorter than that of APP or DAL mice. In addition, they showed accelerated amyloid deposition, tau phosphorylation, and gliosis. Furthermore, these mice showed impaired performance on Y-maze and object recognition tests at 3 months of age. These data suggest that oxidative stress accelerates cognitive dysfunction and pathological insults in the brain. APP/DAL mice could be a useful model for exploring new approaches to AD treatment.