CSF pro-orexin and amyloid-β38 expression in Alzheimer's disease and frontotemporal dementia.
CSF pro-orexin and amyloid-β38 expression in Alzheimer's disease and frontotemporal dementia.
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阿尔茨海默氏病和额颞痴呆症中的CSF亲蛋白和淀粉样蛋白-β38表达。
DOI：
10.1016/j.neurobiolaging.2018.08.019
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发表时间：
2018-12
影响因子：
4.2
通讯作者：
Mills K
中科院分区：
文献类型：
--
作者：
Heywood WE;Hallqvist J;Heslegrave AJ;Zetterberg H;Fenoglio C;Scarpini E;Rohrer JD;Galimberti D;Mills K
对于可以对痴呆的不同形式和亚型进行分层的标记物存在未满足的需求。由于临床表现的相似性，很难区分阿尔茨海默病（AD）和额颞叶痴呆（FTD）。使用多重靶向蛋白质组LC-MS/MS平台，我们旨在鉴定AD和FTD患者之间差异表达的脑脊液蛋白质。此外，对2种经证实携带颗粒蛋白前体（GRN）和9号染色体开放阅读框72（C9 orf 72）突变的FTD遗传亚型进行了分析，以深入了解这些形式FTD的不同病理学。AD患者（n = 13）的食欲素原水平较FTD（n = 32）显著增加（p < 0.007）1.24倍。AD患者的淀粉样β-38水平未发生变化，但FTD组与对照组相比降低>2倍（p < 0.0001），与AD组相比降低1.83倍（p < 0.001）。两个痴呆组的可溶性TREM 2均升高，但AD和FTD之间未显示任何差异。一项比较FTD亚组的进一步分析显示，GRN组（n = 9）的蛋白质载脂蛋白E、CD 166、骨桥蛋白、甲状腺素运载蛋白和胱抑素C水平略低于C9 orf 72组（n = 7）。这些蛋白质表明GRN FTD可改变对C9 orf 72 FTD的炎症反应。
There is an unmet need for markers that can stratify different forms and subtypes of dementia. Because of similarities in clinical presentation, it can be difficult to distinguish between Alzheimer's disease (AD) and frontotemporal dementia (FTD). Using a multiplex targeted proteomic LC-MS/MS platform, we aimed to identify cerebrospinal fluid proteins differentially expressed between patients with AD and FTD. Furthermore analysis of 2 confirmed FTD genetic subtypes carrying progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72) mutations was performed to give an insight into the differing pathologies of these forms of FTD. Patients with AD (n = 13) demonstrated a significant (p < 0.007) 1.24-fold increase in pro-orexin compared to FTD (n = 32). Amyloid beta-38 levels in patients with AD were unaltered but demonstrated a >2-fold reduction (p < 0.0001) in the FTD group compared to controls and a similar 1.83-fold reduction compared to the AD group (p < 0.001). Soluble TREM2 was elevated in both dementia groups but did not show any difference between AD and FTD. A further analysis comparing FTD subgroups revealed slightly lower levels of proteins apolipoprotein E, CD166, osteopontin, transthyretin, and cystatin C in the GRN group (n = 9) compared to the C9orf72 group (n = 7). These proteins imply GRN FTD elicits an altered inflammatory response to C9orf72 FTD.
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脑啡肽酶过度表达可抑制斑块形成，但不能减少人淀粉样前体蛋白转基因小鼠中的致病性 Abeta 寡聚体和相关认知缺陷。
DOI：
10.1523/jneurosci.2984-08.2009
发表时间：
2009-02-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Meilandt WJ;Cisse M;Ho K;Wu T;Esposito LA;Scearce-Levie K;Cheng IH;Yu GQ;Mucke L
通讯作者：
Mucke L
影响因子：
15.9
作者：
Martens, Lauren Henl;Zhang, Jiasheng;Farese, Robert V., Jr.
通讯作者：
Farese, Robert V., Jr.
影响因子：
2.4
作者：
Bibl, Mirko;Mollenhauer, Brit;Wiltfang, Jens
通讯作者：
Wiltfang, Jens
影响因子：
6.8
作者：
Paterson, R. W.;Heywood, W. E.;Schott, J. M.
通讯作者：
Schott, J. M.
影响因子：
15.1
作者：
Heywood WE;Galimberti D;Bliss E;Sirka E;Paterson RW;Magdalinou NK;Carecchio M;Reid E;Heslegrave A;Fenoglio C;Scarpini E;Schott JM;Fox NC;Hardy J;Bhatia K;Heales S;Sebire NJ;Zetterberg H;Mills K
通讯作者：
Mills K