Toft Anders, Sjödin Simon, Simonsen Anja Hviid, Ejlerskov Patrick, Roos Peter, Musaeus Christian Sandøe, Henriksen Emil Elbæk, Nielsen Troels Tolstrup, Brinkmalm Ann, Blennow Kaj, Zetterberg Henrik, Nielsen Jørgen Erik
Neurogenetics Clinic & Research Lab Danish Dementia Research Centre Rigshospitalet Copenhagen Denmark.
Laboratory of Clinical Chemistry Sahlgrenska University Hospital Gothenburg Sweden.
Alzheimers Dement (Amst). 2023 Feb 16;15(1):e12402. doi: 10.1002/dad2.12402. eCollection 2023 Jan-Mar.
Increasing evidence implicates proteostatic dysfunction as an early event in the development of frontotemporal dementia (FTD). This study aimed to explore potential cerebrospinal fluid (CSF) biomarkers associated with the proteolytic systems in genetic FTD caused by mutation.
Combining solid-phase extraction and parallel reaction monitoring mass spectrometry, a panel of 47 peptides derived from 20 proteins was analyzed in CSF from 31 members of the Danish -FTD family.
Compared with family controls, mutation carriers had significantly higher levels of complement C9, lysozyme and transcobalamin II, and lower levels of ubiquitin, cathepsin B, and amyloid precursor protein.
Lower CSF ubiquitin concentrations in mutation carriers indicate that ubiquitin levels relate to the specific disease pathology, rather than all-cause neurodegeneration. Increased lysozyme and complement proteins may indicate innate immune activation. Altered levels of amyloid precursor protein and cathepsins have previously been associated with impaired lysosomal proteolysis in FTD.
CSF markers of proteostasis were explored in -mediated frontotemporal dementia (FTD).31 members of the Danish -FTD family were included.We used solid-phase extraction and parallel reaction monitoring mass spectrometry.Six protein levels were significantly altered in -FTD compared with controls.Lower CSF ubiquitin levels in patients suggest association with disease mechanisms.
越来越多的证据表明蛋白质稳态功能障碍是额颞叶痴呆（FTD）发病的早期事件。本研究旨在探索与由突变引起的遗传性FTD中蛋白水解系统相关的潜在脑脊液（CSF）生物标志物。
结合固相萃取和平行反应监测质谱法，对来自丹麦FTD家族31名成员的脑脊液中的一组由20种蛋白质衍生的47种肽进行了分析。
与家族对照相比，突变携带者的补体C9、溶菌酶和转钴胺素II水平显著升高，而泛素、组织蛋白酶B和淀粉样前体蛋白水平降低。
突变携带者脑脊液中泛素浓度降低表明泛素水平与特定疾病病理相关，而非与全因神经退行性变相关。溶菌酶和补体蛋白增加可能表明先天免疫激活。淀粉样前体蛋白和组织蛋白酶水平的改变此前已与FTD中溶酶体蛋白水解受损相关。
在介导的额颞叶痴呆（FTD）中探索了蛋白质稳态的脑脊液标志物。纳入了丹麦FTD家族的31名成员。我们使用了固相萃取和平行反应监测质谱法。与对照组相比，FTD中有六种蛋白质水平发生了显著改变。患者脑脊液中泛素水平降低表明与疾病机制有关。
