Ảnh hưởng của các biến thể rủi ro TREM2 đến sự kích hoạt miễn dịch theo vùng não và môi trường vi mô của mảng bám trong mẫu não của bệnh nhân Alzheimer

Springer Science and Business Media LLC - Tập 138 - Trang 613-630 - 2019
Stefan Prokop1,2,3,4, Kelly R. Miller1,5, Sergio R. Labra1, Rose M. Pitkin1, Kevt’her Hoxha1, Sneha Narasimhan1, Lakshmi Changolkar1, Alyssa Rosenbloom5, Virginia M.-Y. Lee1, John Q. Trojanowski1
1Department of Pathology and Laboratory Medicine, AD Center Core (ADCC), Center for Neurodegenerative Disease Research, University of Pennsylvania (PENN) School of Medicine, Philadelphia, USA
2Department of Pathology, University of Florida, Gainesville, USA
3Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, USA
4Fixel Institute for Neurological Diseases, University of Florida, Gainesville, USA
5NanoString Technologies, Seattle, USA

Tóm tắt

Việc xác định nhiều yếu tố di truyền có liên quan đến miễn dịch gây rủi ro cho Alzheimer thể tự phát (sAD) đã đưa hệ thống miễn dịch vào trung tâm của các cơ chế nền tảng cho rối loạn này. Phân tích toàn diện về tế bào viêm màng não (microglia) ở các giai đoạn khác nhau của Alzheimer trong não người đã chỉ ra rằng việc kích hoạt microglia xảy ra theo sự tiến triển của những biến đổi bệnh lý thần kinh liên quan đến Alzheimer và yêu cầu sự đồng thời của các bệnh lý về beta-Amyloid (Aβ) và tau. Những người mang các biến thể rủi ro liên quan đến Alzheimer ở gen TREM2 (Thụ thể kích hoạt biểu hiện trên tế bào tiền thân myeloid 2) cho thấy sự giảm bớt của microglia liên quan đến mảng bám và một sự gia tăng đáng kể của các sợi thần kinh thoái hóa cũng như tổng thể tau bệnh lý so với những bệnh nhân Alzheimer đồng nhất về độ tuổi và giai đoạn bệnh mà không có biến thể rủi ro TREM2. Những phát hiện này đã được chứng minh bằng việc phân tích khu vực vi mô kỹ thuật số của môi trường mảng bám và phân tích biểu hiện gen có mục tiêu trên hệ thống NanoString nCounter, đã cho thấy sự khác biệt đáng kể về mô hình phản ứng miễn dịch theo vùng não trong các trường hợp cá thể. Việc chứng minh sự khác biệt sâu sắc theo vùng não và theo biến thể rủi ro trong kích hoạt miễn dịch trong não người mắc bệnh Alzheimer tác động đến tính khả thi của các phương pháp điều trị miễn dịch cho sAD và các bệnh thoái hóa thần kinh liên quan.

Từ khóa

#Alzheimer #TREM2 #viêm màng não #mảng bám #cơ chế bệnh lý

Tài liệu tham khảo

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