More and more data from preclinical and clinical studies strengthen the hypothesis that immune system-mediated actions contribute to and drive pathogenesis in Alzheimer’s disease. New insights suggest that A? indeed induces a strong inflammatory response, thereby destroying an important but often neglected brain barrier, called the blood-cerebrospinal fluid (CSF) barrier. Disruption of this blood-CSF barrier disturbs brain homeostasis and might negatively affect disease progression. Strikingly, these effects could be blocked in the presence of a matrix metalloproteinase (MMP) inhibitor.