Potent amyloidogenicity and pathogenicity of Aβ43.

• Saito, Takashi

• Suemoto, Takahiro

• Brouwers, Nathalie

• Sleegers, Kristel

• Funamoto, Satoru

• Mihira, Naomi

• Matsuba, Yukio

• Yamada, Kazuyuki

• Nilsson, Per

• Takano, Jiro

• Nishimura, Masaki

• Iwata, Nobuhisa

• Van, Broeckhoven Christine

• Ihara, Yasuo

• Saido, Takaomi C

抄録

The amyloid-β peptide Aβ42 is known to be a primary amyloidogenic and pathogenic agent in Alzheimer's disease. However, the role of Aβ43, which is found just as frequently in the brains of affected individuals, remains unresolved. We generated knock-in mice containing a pathogenic presenilin-1 R278I mutation that causes overproduction of Aβ43. Homozygosity was embryonic lethal, indicating that the mutation involves a loss of function. Crossing amyloid precursor protein transgenic mice with heterozygous mutant mice resulted in elevated Aβ43, impairment of short-term memory and acceleration of amyloid-β pathology, which accompanied pronounced accumulation of Aβ43 in plaque cores similar in biochemical composition to those observed in the brains of affected individuals. Consistently, Aβ43 showed a higher propensity to aggregate and was more neurotoxic than Aβ42. Other pathogenic presenilin mutations also caused overproduction of Aβ43 in a manner correlating with Aβ42 and with the age of disease onset. These findings indicate that Aβ43, an overlooked species, is potently amyloidogenic, neurotoxic and abundant in vivo.

Nature Neuroscience, 14(8), pp.1023-1032; 2011

収録刊行物

• Nature Neuroscience

  Nature Neuroscience 14 (8), 1023-1032, 2011-08

  Nature Publishing Group

キーワード

• General Neuroscience

詳細情報

• CRID: 1050568772228255488
• NII論文ID: 120006985066
• NII書誌ID: AA11202192
• ISSN: 10976256
• ISSN: 15461726
• DOI: 10.1038/nn.2858
• HANDLE: 10069/27387
• Web Site: https://nagasaki-u.repo.nii.ac.jp/records/13465
• Web Site: http://www.nature.com/articles/nn.2858.pdf
• Web Site: http://www.nature.com/articles/nn.2858
• 本文言語コード: en
• 資料種別: journal article
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