The levels of water-soluble and triton-soluble A尾 are increased in Alzheimer's disease brain

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• 作者：Jessica M. McDonald^a ; Nigel J. Cairns^b ; Lisa Taylor-Reinwald^b ; David Holtzman^b ; Dominic M. Walsh^a ; ^{dwalsh3@partners.org}
• 关键词：AD ; Alzheimer's disease ; A尾 ; amyloid 尾-protein ; TBS ; Tris-buffered saline ; TBS-TX ; TBS containing 1%TX-100 ; FA ; formic acid ; IP ; immunoprecipitation ; CDR ; clinical dementia rating
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：23 April, 2012
• 卷：1450
• 期：Complete
• 页码：138-147
• 文件大小：682 K

摘要

Although plaques composed of the amyloid 尾-protein (A尾) are considered a defining feature of Alzheimer's disease (AD), they are also found in cognitively normal individuals and extensive evidence suggests that non-plaque, water-soluble forms of A尾 may play a role in AD pathogenesis. However, the relationship between the levels of water-soluble A尾 and the clinical severity of disease has never been investigated. Here, we present results of a pilot study designed to examine the levels of water-soluble forms of A尾 in brains of individuals who died at clinically distinct stages of AD. Using a serial extraction method, we also investigated the levels of triton-soluble and formic acid-soluble A尾. We found that water-soluble and detergent-soluble A尾 monomer and SDS-stable dimer were elevated in AD and that the levels of water soluble A尾 did not increase with plaque pathology. These results support the notion that both water- and detergent-soluble A尾 are important in AD and are not simply released from plaques by mechanical disruption. Moreover, the fact that the levels of water- and triton-soluble A尾 were similar in very mild/mild AD and moderate/severe AD suggests that once a certain level of these species is attained, further accumulation is not necessary for the disease to progress. Consequently, therapeutic targeting of water-soluble A尾 should best benefit individuals in earliest phases of the disease process.