Những người không bị suy giảm nhận thức với gánh nặng Aβ thấp có hồ sơ sinh học chất lỏng não tủy khác biệt

Springer Science and Business Media LLC - 2021
Marta Milà‐Alomà1, Mahnaz Shekari2,1, Gemma Salvadó1, Juan Domingo Gispert1, Eider M. Arenaza‐Urquijo1, Grégory Operto1, Carles Falcón1, Natàlia Vilor‐Tejedor1, Oriol Grau‐Rivera1, Aleix Sala‐Vila1, Gonzalo Sánchez‐Benavides1, José María González‐de‐Echávarri1, Carolina Minguillón1, Karine Fauria1, Aida Niñerola‐Baizán3, Andrés Perissinotti3, Maryline Simon4, Gwendlyn Kollmorgen5, Henrik Zetterberg6, Kaj Blennow7,8, Marc Suárez‐Calvet9, José Luís Molinuevo10,11
1Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Wellington 30, 08005, Barcelona, Spain.
2Universitat Pompeu Fabra, Barcelona, Spain
3Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain
4Roche Diagnostics International Ltd, Rotkreuz, Switzerland
5Roche Diagnostics GmbH, Penzberg, Germany
6Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Molndal, Sweden
7Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden
8Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
9Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Wellington 30, 08005, Barcelona, Spain. [email protected].
10Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Wellington 30, 08005, Barcelona, Spain. [email protected].
11Present address: H. Lundbeck A/S, Copenhagen, Denmark. [email protected].

Tóm tắt

Tóm tắt Đặt vấn đề Hiểu những thay đổi xảy ra trong giai đoạn chuyển tiếp giữa tình trạng không có và tình trạng có amyloid-β (Aβ) rõ ràng trong tiếp diễn của bệnh Alzheimer là rất quan trọng để phát triển các chiến lược điều trị và phòng ngừa. Mục tiêu của nghiên cứu này là kiểm tra xem liệu những người không bị suy giảm nhận thức với gánh nặng Aβ thấp có một hồ sơ dấu ấn sinh học chất lỏng não tủy (CSF), hình ảnh não cấu trúc và chức năng khác biệt hay không. Phương pháp Nghiên cứu cắt ngang với 318 cá nhân trung niên không bị suy giảm nhận thức từ nhóm ALFA+. Chúng tôi đã đo CSF Aβ42/40, tau phosphoryl hóa (p-tau), tau tổng (t-tau), neurofilament nhẹ (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100B, và α-synuclein. Các đối tượng cũng đã trải qua các đánh giá nhận thức, phân tích gen APOE, MRI cấu trúc, [18F]-FDG, và [18F]-flutemetamol PET. Để đảm bảo tính chính xác của kết quả, chúng tôi đã sử dụng ba định nghĩa về gánh nặng Aβ thấp: (1) CSF Aβ42/40 dương tính và < 30 Centiloids trong PET Aβ, (2) CSF Aβ42/40 dương tính và đọc hình ảnh Aβ PET âm tính, và (3) phạm vi 20–40 Centiloid trong PET Aβ. Chúng tôi đã kiểm tra sự khác biệt về CSF và dấu ấn sinh học hình ảnh não giữa nhóm gánh nặng thấp và nhóm Aβ âm tính tương ứng, đã điều chỉnh theo tuổi và giới. Kết quả Tỷ lệ và đặc điểm nhân khẩu học của nhóm gánh nặng thấp khác nhau giữa ba định nghĩa. CSF p-tau và t-tau tăng lên ở nhóm gánh nặng thấp so với Aβ âm tính trong tất cả các định nghĩa. CSF neurogranin tăng lên trong nhóm gánh nặng thấp theo định nghĩa 1 và 3, trong khi CSF NfL chỉ tăng lên trong nhóm gánh nặng thấp theo định nghĩa 1. Không có nhóm gánh nặng thấp nào cho thấy dấu hiệu teo hoặc chuyển hóa glucose giảm. Thay vào đó, chúng tôi phát hiện những tăng nhẹ về độ dày vỏ não và chuyển hóa trong định nghĩa 2. Kết luận Có những tác động sinh học có ý nghĩa về Aβ downstream ở những cá nhân có gánh nặng Aβ thấp, trong khi những thay đổi cấu trúc và chức năng vẫn còn tinh tế hoặc không có. Những phát hiện này ủng hộ việc xem xét những cá nhân có gánh nặng Aβ thấp cho các thử nghiệm lâm sàng. Đăng ký thử nghiệm NCT02485730

Từ khóa


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