研究揭示與漸進(jìn)性Aβ斑塊和tau纏結(jié)病理相關(guān)的阿爾茨海默病蛋白質(zhì)組學(xué)變化

作者：小柯機(jī)器人 發(fā)布時(shí)間：2024/8/28 15:04:01

本期文章：《自然—神經(jīng)科學(xué)》：Online/在線發(fā)表

瑞典隆德大學(xué)Oskar Hansson等研究人員合作揭示，與漸進(jìn)性Aβ斑塊和tau纏結(jié)病理相關(guān)的阿爾茨海默病蛋白質(zhì)組學(xué)變化。相關(guān)論文于2024年8月26日在線發(fā)表在《自然—神經(jīng)科學(xué)》雜志上。

結(jié)合放射性配體測(cè)量β-淀粉樣蛋白（Aβ）斑塊和tau纏結(jié)與腦脊液蛋白質(zhì)組學(xué)分析，研究人員發(fā)現(xiàn)了反映阿爾茨海默?。ˋD）病理不同階段的分子事件。在整個(gè)AD譜系中，研究人員發(fā)現(xiàn)了127種差異豐富的蛋白質(zhì)（DAP）。

最強(qiáng)的Aβ相關(guān)蛋白主要在膠質(zhì)細(xì)胞中表達(dá)，包括SMOC1和ITGAM。與tau纏結(jié)負(fù)荷和tau積累獨(dú)立相關(guān)的有十幾種與ATP代謝相關(guān)并優(yōu)先在神經(jīng)元中表達(dá)的蛋白質(zhì)。

僅有20%的DAP在其他神經(jīng)退行性疾病中也發(fā)生變化，突顯出AD獨(dú)特的蛋白質(zhì)組特征。與蛋白質(zhì)代謝和小膠質(zhì)細(xì)胞免疫反應(yīng)相關(guān)的兩個(gè)共表達(dá)模塊包含了大多數(shù)DAP，并沿著AD連續(xù)體表現(xiàn)出相反的、錯(cuò)位的軌跡。

研究人員揭示了與Aβ和tau蛋白病相關(guān)的體內(nèi)蛋白質(zhì)特征，為復(fù)雜的神經(jīng)反應(yīng)以及針對(duì)不同疾病階段的潛在生物標(biāo)志物和治療手段提供了新的見解。

據(jù)介紹，蛋白質(zhì)組學(xué)能夠揭示像AD這樣復(fù)雜的神經(jīng)退行性疾病中的動(dòng)態(tài)和多方面的變化。

附：英文原文

Title: Proteomic changes in Alzheimer disease associated with progressive Aβ plaque and tau tangle pathologies

Author: Pichet Binette, Alexa, Gaiteri, Chris, Wennstrm, Malin, Kumar, Atul, Hristovska, Ines, Spotorno, Nicola, Salvad, Gemma, Strandberg, Olof, Mathys, Hansruedi, Tsai, Li-Huei, Palmqvist, Sebastian, Mattsson-Carlgren, Niklas, Janelidze, Shorena, Stomrud, Erik, Vogel, Jacob W., Hansson, Oskar

Issue&Volume: 2024-08-26

Abstract: Proteomics can shed light on the dynamic and multifaceted alterations in neurodegenerative disorders like Alzheimer disease (AD). Combining radioligands measuring β-amyloid (Aβ) plaques and tau tangles with cerebrospinal fluid proteomics, we uncover molecular events mirroring different stages of AD pathology in living humans. We found 127 differentially abundant proteins (DAPs) across the AD spectrum. The strongest Aβ-related proteins were mainly expressed in glial cells and included SMOC1 and ITGAM. A dozen proteins linked to ATP metabolism and preferentially expressed in neurons were independently associated with tau tangle load and tau accumulation. Only 20% of the DAPs were also altered in other neurodegenerative diseases, underscoring AD’s distinct proteome. Two co-expression modules related, respectively, to protein metabolism and microglial immune response encompassed most DAPs, with opposing, staggered trajectories along the AD continuum. We unveil protein signatures associated with Aβ and tau proteinopathy in vivo, offering insights into complex neural responses and potential biomarkers and therapeutics targeting different disease stages.

DOI: 10.1038/s41593-024-01737-w

Source: https://www.nature.com/articles/s41593-024-01737-w

期刊信息

Nature Neuroscience：《自然—神經(jīng)科學(xué)》，創(chuàng)刊于1998年。隸屬于施普林格·自然出版集團(tuán)，最新IF：28.771

官方網(wǎng)址：https://www.nature.com/neuro/

投稿鏈接：https://mts-nn.nature.com/cgi-bin/main.plex