（Fig.1 Flotillin-mediated endocytosis and ESCRT-mediated exocytosis independently repair cell membrane that’s damaged by p-MLKL during necroptosis）

(Fig. 2 p-MLKL signal was highly accumulated in the hippocampal neuron in Alzheimer’s patients’ autopsy samples)

Current work also discovered the existence of polymorphism on the MLKL-binding region of Flotilin-1 protein. Some of which would block the Flotilllin-1 mediated MLKL degradation. This pathway may also play key roles in the pathology of Alzheimer’s disease. In current work, in corroboration with Dr Jing Zhang（Department of Pathology, University of Washington School of Medicine, Seattle, WA；Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing）and Ms. Hua Wang (Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center；Department of Pathology, Peking University Third Hospital, Beijing），<span color:black;"="" style="line-height:150%">Dr. Wang’s lab discovered that hippocampal neurons accumulated significantly more p-MLKL signal in the Alzheimer’s patients’ autopsy sample than control patient at similar age. Majority of these p-MLKL signals were in colocalization with Flotillin within the cytosol of these neurons.

Dr.Weiliang Fan, a postdoctoral fellow in Dr. Wang’s lab is the leading author of the study. Other authors include Dr. Jia Guo, Beichen Gao (former technician, now PhD student), Wenbin Zhang (PhD student), Liucong Ling (former technician), Tao Xu (former technician), Chenjie Pan (Now postdoctoral fellow at Harvard medical school), Lin Li, Dr.She Chen, Dr.Jing Zhang (Professor at Department of Pathology, University of Washington School of Medicine, Seattle, WA；Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing), Hua Wang (Doctor at Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center；Department of Pathology, Peking University Third Hospital, Beijing). Dr.Xiaodong Wang is the corresponding author. Great help has been given by Yue Sun and Dr. Cheng Zhan from the microscopic facility, Dr. Zhaodi Jiang from the electron microscopic facility at the National Institute of Biological Sciences, Beijing. This work was supported by National Basic Science 973 grant no. 2010CB835400 from the Chinese Ministry of Science and Technology. W.F. was supported by an Amgen-China postdoctoral fellowship from 2014 to 2018.