Heneka Michael T, van der Flier Wiesje M, Jessen Frank, Hoozemanns Jeroen, Thal Dietmar Rudolf, Boche Delphine, Brosseron Frederic, Teunissen Charlotte, Zetterberg Henrik, Jacobs Andreas H, Edison Paul, Ramirez Alfredo, Cruchaga Carlos, Lambert Jean-Charles, Laza Agustin Ruiz, Sanchez-Mut Jose Vicente, Fischer Andre, Castro-Gomez Sergio, Stein Thor D, Kleineidam Luca, Wagner Michael, Neher Jonas J, Cunningham Colm, Singhrao Sim K, Prinz Marco, Glass Christopher K, Schlachetzki Johannes C M, Butovsky Oleg, Kleemann Kilian, De Jaeger Philip L, Scheiblich Hannah, Brown Guy C, Landreth Gary, Moutinho Miguel, Grutzendler Jaime, Gomez-Nicola Diego, McManus Róisín M, Andreasson Katrin, Ising Christina, Karabag Deniz, Baker Darren J, Liddelow Shane A, Verkhratsky Alexei, Tansey Malu, Monsonego Alon, Aigner Ludwig, Dorothée Guillaume, Nave Klaus-Armin, Simons Mikael, Constantin Gabriela, Rosenzweig Neta, Pascual Alberto, Petzold Gabor C, Kipnis Jonathan, Venegas Carmen, Colonna Marco, Walter Jochen, Tenner Andrea J, O'Banion M Kerry, Steinert Joern R, Feinstein Douglas L, Sastre Magdalena, Bhaskar Kiran, Hong Soyon, Schafer Dorothy P, Golde Todd, Ransohoff Richard M, Morgan David, Breitner John, Mancuso Renzo, Riechers Sean-Patrick
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette/Belvaux, Luxembourg.
Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
Nat Rev Immunol. 2025 May;25(5):321-352. doi: 10.1038/s41577-024-01104-7. Epub 2024 Dec 9.
Increasing evidence points to a pivotal role of immune processes in the pathogenesis of Alzheimer disease, which is the most prevalent neurodegenerative and dementia-causing disease of our time. Multiple lines of information provided by experimental, epidemiological, neuropathological and genetic studies suggest a pathological role for innate and adaptive immune activation in this disease. Here, we review the cell types and pathological mechanisms involved in disease development as well as the influence of genetics and lifestyle factors. Given the decade-long preclinical stage of Alzheimer disease, these mechanisms and their interactions are driving forces behind the spread and progression of the disease. The identification of treatment opportunities will require a precise understanding of the cells and mechanisms involved as well as a clear definition of their temporal and topographical nature. We will also discuss new therapeutic strategies for targeting neuroinflammation, which are now entering the clinic and showing promise for patients.
越来越多的证据表明，免疫过程在阿尔茨海默病的发病机制中起关键作用，阿尔茨海默病是当今最常见的神经退行性疾病和导致痴呆的疾病。实验、流行病学、神经病理学和遗传学研究提供的多条信息表明，先天性和适应性免疫激活在该疾病中具有病理作用。在这里，我们回顾了疾病发展过程中涉及的细胞类型和病理机制，以及遗传和生活方式因素的影响。鉴于阿尔茨海默病长达十年的临床前期，这些机制及其相互作用是疾病传播和进展的驱动力。确定治疗机会将需要精确了解所涉及的细胞和机制，以及对其时间和空间性质的明确定义。我们还将讨论针对神经炎症的新治疗策略，这些策略目前正在进入临床并显示出对患者的希望。
