The Arctic amyloid-尾 precursor protein (A尾PP) mutation results in distinct plaques and accumulation of N- and C-truncated A尾

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• 作者：Ola Philipson^a ; Anna Lord^a ; ^j ; Maciej Lalowski^b ; Rabah Soliymani^b ; Marc Baumann^b ; Johan Thyberg^c ; Nenad Bogdanovic^d ; ^e ; Tommie Olofsson^f ; ^g ; Lars O. Tjernberg^d ; Martin Ingelsson^a ; Lars Lannfelt^a ; Hannu Kalimo^h ; ⁱ ; Lars N.G. Nilsson^a ; ^k ; ^{lars.nilsson@medisin.uio.no}
• 关键词：Alzheimer's disease ; A尾PP mutation ; 尾-amyloid protein ; Familial ; Mass spectrometry ; N-terminal truncation ; Neuropathology
• 刊名：Neurobiology of Aging
• 出版年：2012
• 期刊代码：202_01974580
• 类别：med
• 出版时间：May, 2012
• 卷：33
• 期：5
• 页码：1010.e1-1010.e13
• 文件大小：4049 K

摘要

The Arctic (p. E693G) mutation in the amyloid-尾 precursor protein (A尾PP) facilitates amyloid-尾 (A尾) protofibril formation and generates clinical symptoms of Alzheimer's disease (AD). Here, molecular details of A尾 in post mortem brain were investigated with biochemical and morphological techniques. The basic structure of Arctic plaques resembled cotton wool plaques. However, they appeared ring-formed with A尾42-specific antibodies, but were actually targetoid, since the periphery and center of many parenchymal A尾 deposits stained differently with mid-domain, N- and C-terminal A尾 antibodies. A尾 fibrils were similar in shape, albeit shorter than in sporadic AD brain, when examined by electron microscopy. A尾wild-type and A尾arctic codeposited and parenchymal deposits were highly enriched in both N- and C-terminally truncated A尾. In contrast, cerebral amyloid angiopathy (CAA) contained a substantial amount of A尾1-40. The absence of plaques with cores of fibrillary A尾 might be due to the scarcity of full-length A尾, although other mechanisms could be involved. Our findings are discussed in relation to mechanisms and relevance of amyloid formation and to the clinical features of AD.