Researchers at LSU Health New Orleans Neuroscience Center of Excellence and Karolinska Institutet have discovered a potential biomarker for Alzheimer’s disease diagnosis that may also serve as a therapeutic target. Examining cerebrospinal fluid samples from patients with cognitive impairment ranging from subjective impairment to a diagnosis of Alzheimer’s disease, they found a shift in the profile of specialized lipid mediators from pro-resolving to pro-inflammatory. The results of the exploratory study are published in the Springer journal,Cellular and Molecular Neurobiology, availablehere。

专门的脂质介质是由DHA和EPA等多不饱和脂肪酸组成的生物活性化合物。它们是信号分子，可调节广泛的细胞反应，包括细胞生长和死亡以及感染和炎症。专门的脂质介质具有独特的特性和在炎症中的作用。促炎性脂质介质会促进炎症，并促脂质脂质介质解决炎症。

阿尔茨海默氏病（AD）需要几年或更长时间才能发展成痴呆症，而神经炎症是重要的早期贡献者。在此期间，主观认知障碍（SCI）和轻度认知障碍（MCI）可用作严重程度增加的中介诊断。这项研究的人群由136名参与者组成 - 53名SCI，43个具有MCI的参与者和40个参与者，有40个参与者，以及阿尔茨海默氏病的诊断。研究人员评估了参与者脑脊液（CSF）样品中的22种脂质，包括促脂质脂质介质，促炎性脂质介质，前列腺素，其脂肪酸前体和中间衍生物。神经保护D1（NPD1）, discovered by the Bazan lab, is one the pro-resolving lipid mediators studied.

研究小组发现，促溶解脂质介质的水平与认知障碍的严重程度相关 - 严重程度越大，解决炎症的脂质介质的水平越低。他们还发现认知障碍的严重程度与促炎性脂质介质之间存在关系 - 认知障碍的程度越大，促进炎症的脂质介质的水平越高。

“Based on these findings, we are expanding our work to brain cell-specific targets, besides neurons, astrocytes and microglia, as well as additional novel protective signals, which would allow us to explore slowing down AD onset,” says Nicolas Bazan, MD, PhD, Boyd Professor and Director of LSU Health New Orleans Neuroscience Center of Excellence. “For this purpose, we have set up 10-x genomics to decipher not only the genes but also epigenomics engaged in early disease states. Since the CSF lipidome changes were closely correlated with detailed clinical and radiological AD patient status, we believe that the studied events are revealing novel essential mechanisms of brain health. A uniqueness of our approach is that we have discovered mechanisms and, more importantly, molecules that target those mechanisms and could became therapeutics.”

Other members of the LSU Health New Orleans research team include Drs. Khanh V. Do, Bokkyoo Jun, and Marie-Audrey I. Kautzmann. Ceren Emre, who recently completed her PhD at the Karolinska Institutet, worked at LSU Health New Orleans Neuroscience Center of Excellence for eight months before the pandemic. Other researchers from the Karolinska Institutet include Drs. Erik Hjorth, Ying Wang, Makiko Ohshima, Maria Eriksdotter, and Senior Professor Marianne Schultzberg, Bazan’s key collaborator.

Reference:Do KV，Hjorth E，Wang Y等。阿尔茨海默氏病中脂质介质的脑脊液谱。细胞摩尔神经生物学。2022. doi：10.1007/S10571-022-01216-5

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