Spatiotemporal development of the neuronal accumulation of amyloid precursor protein and the amyloid plaque formation in the brain of 3xTg-AD mice
Munenori Ono,
Tetsufumi Ito,
Sachiko Yamaki,
Yoshie Hori,
Qing Zhou,
Xirun Zhao,
Shinji Muramoto,
Ryo Yamamoto,
Takafumi Furuyama,
Hiromi Sakata-Haga,
Toshihisa Hatta,
Tsuyoshi Hamaguchi,
Nobuo Kato
Affiliations
Munenori Ono
Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan; Corresponding author. Department of Physiology, School of Medicine, Kanazawa Medical University, Uchinada, Ishikawa, 920-0293, Japan.
Tetsufumi Ito
Systems Function and Morphology, University of Toyama, Toyama, 930-0194, Japan
Sachiko Yamaki
Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan
Yoshie Hori
Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan
Qing Zhou
Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan
Xirun Zhao
Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan
Shinji Muramoto
Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan
Ryo Yamamoto
Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan
Takafumi Furuyama
Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan
Hiromi Sakata-Haga
Department of Anatomy, Kanazawa Medical University, Ishikawa, 920-0293, Japan
Toshihisa Hatta
Department of Anatomy, Kanazawa Medical University, Ishikawa, 920-0293, Japan
Tsuyoshi Hamaguchi
Department of Neurology, Kanazawa Medical University, Ishikawa, 920-0293, Japan
Nobuo Kato
Department of Physiology, Kanazawa Medical University, Ishikawa, 920-0293, Japan
The amyloid plaque is a hallmark of Alzheimer's disease. The accumulation of the amyloid precursor protein (APP) in the neuronal structure is assumed to lead to amyloid plaque formation through the excessive production of β-amyloid protein. To study the relationship between the neuronal accumulation of APP and amyloid plaque formation, we histologically analyzed their development in the different brain regions in 3xTg-AD mice, which express Swedish mutated APP (APPSWE) in the neurons. Observation throughout the brain revealed APPSWE-positive somata in the broad regions. Quantitative model analysis showed that the somatic accumulation of APPSWE developed firstly in the hippocampus from a very early age (<1 month) and proceeded slower in the isocortex. In line with this, the hippocampus was the first region to form amyloid plaques at the age of 9–12 months, while amyloid plaques were rarely observed in the isocortex. Females had more APPSWE-positive somata and plaques than males. Furthermore, amyloid plaques were observed in the lateral septum and pontine grey, which did not contain APPSWE-positive somata but only the APPSWE-positive fibers. These results suggested that neuronal accumulation of APPSWE, both in somatodendritic and axonal domains, is closely related to the formation of amyloid plaques.
