Fernandes Gomes Bárbara, Kumar Atul, Ashton Nicholas J, Hall Sara, Stomrud Erik, Smith Ruben, Zetterberg Henrik, Blennow Kaj, Mattsson-Carlgren Niklas, Hansson Oskar
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 43180 Mölndal, Sweden.
Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, 20213 Malmö, Sweden.
Brain Commun. 2024 Nov 19;6(6):fcae414. doi: 10.1093/braincomms/fcae414. eCollection 2024.
Disease-specific fluid biomarkers are in demand for parkinsonian syndromes (PS). Corticotropin-releasing hormone (CRH) was proposed as a biomarker for Lewy body disease. As such, this project aimed to confirm CRH as a potential biomarker for different PS. CRH and misfolded α-synuclein (αSyn) were measured in CSF. The primary cohort included Lewy body disease patients (i.e. Parkinson's disease or dementia with Lewy bodies, = 77), atypical PS ( = 37) and non-parkinsonian neurodegenerative diseases ( = 164), as well as controls ( = 354). A replication cohort included Lewy body disease ( = 27), atypical PS ( = 58) and controls ( = 58). CRH was downregulated in αSyn positive Lewy body disease, αSyn positive controls and in all atypical PS compared with αSyn negative controls ( = 3.3e-05, = 3.1e-10, = 2.9e-03). CRH was also decreased in αSyn positive Lewy body disease compared with αSyn negative non-PS ( = 2e-03) and correlated with cognitive impairment and inflammation in αSyn positive Lewy body disease. We show that CRH is a promising biomarker for Lewy body disease and atypical PS and its association with inflammation and cognitive decline. Reductions in CRH in Lewy body disease and other PS suggest this decrease may relate to dopaminergic degeneration instead of αSyn pathology.
帕金森综合征（PS）需要疾病特异性的体液生物标志物。促肾上腺皮质激素释放激素（CRH）被提议作为路易体病的生物标志物。因此，本项目旨在确认CRH作为不同PS的潜在生物标志物。在脑脊液中测量了CRH和错误折叠的α-突触核蛋白（αSyn）。主要队列包括路易体病患者（即帕金森病或路易体痴呆，n = 77）、非典型PS（n = 37）和非帕金森神经退行性疾病（n = 164），以及对照组（n = 354）。复制队列包括路易体病（n = 27）、非典型PS（n = 58）和对照组（n = 58）。与αSyn阴性对照组相比，αSyn阳性的路易体病、αSyn阳性对照组和所有非典型PS中CRH均下调（P = 3.3e - 05，P = 3.1e - 10，P = 2.9e - 03）。与αSyn阴性的非PS相比，αSyn阳性的路易体病中CRH也降低（P = 2e - 03），并且在αSyn阳性的路易体病中与认知障碍和炎症相关。我们表明，CRH是路易体病和非典型PS的有前景的生物标志物，以及其与炎症和认知衰退的关联。路易体病和其他PS中CRH的降低表明这种减少可能与多巴胺能变性而非αSyn病理有关。
