Type-specific evolution of amyloid plaque and angiopathy in APPsw mice |
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Authors: | Yasuo Harigaya Yasushi Tomidokoro Masaki Ikeda Atsushi Sasaki Takeshi Kawarabayashi Etsuro Matsubara Mitsuyasu Kanai Takaomi C Saido Steven G Younkin Mikio Shoji |
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Institution: | 1. Neurology Service, Maebashi Red Cross Hospital, 3-21-36, Asahi-cho, Maebashi, Gunma 371-0014, Japan;2. Department of Neurology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan;3. First Department of Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan;4. Department of Neurology, Neuroscience, Biophysiological Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikada-cho, Okayama 700-8558, Japan;5. Department of Alzheimer''s Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka-machi, Obu, Aichi 474-8522, Japan;6. The Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan;g Department of Pharmacology and Pathology, Mayo Clinic Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224, USA |
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Abstract: | To clarify how Aβ deposits start in the brain, we examined the early to late stages of senile plaques and amyloid angiopathy in APPsw mice. All types of human senile plaques were observed in the mouse brains. The premature forms of cored plaques appeared first in the cerebral cortex of mice at 7–8 months old. Then, amyloid angiopathy emerged, followed by diffuse plaques consisting of Aβ1–42. Modifications of the N-terminus of Aβ were late phase phenomena. The premature forms of cored plaques were composed of central Aβ1–40 amyloid cores, surrounding amorphous Aβ1–42 deposits, and accumulation of Aβ1–42 in some peripheral cells. These cells were incorporated in amyloid cores, and these plaques developed to large cored plaques composed of Aβ1–40 and Aβ1–42. The size and number of cored plaques were increased with age. These findings indicate different evolution paths for cored plaques and diffuse plaques, and suggest the presence of a pathway that initiates with the intracellular accumulation of Aβ1–42 and leads to the development of classic plaques in human brain tissues. |
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Keywords: | Alzheimer's disease Aβ42 Aβ40 Amyloid angiopathy Cored plaques Diffuse plaques Transgenic mice |
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