We focus on Alzheimer’s disease (AD) animal models and their susceptibility to barrier leakage based on age and genetic background; on barrier dysfunction in clinical and postmortem studies; summarize changes that lead to barrier leakage in patients; and highlight the clinical relevance of barrier leakage in AD. We summarize signaling mechanisms that link barrier leakage to neurodegeneration and cognitive decline in AD. We discuss clinical relevance and potential therapeutic strategies and provide future perspectives on investigating barrier leakage in AD.
