Blood-Brain Barrier Remains Intact in Common Alzheimer's Disease Model, Challenging Old Beliefs

Recent research from Texas Tech University Health Sciences Center (TTUHSC) has provided new insights into the integrity of the blood-brain barrier (BBB) in Alzheimer's disease (AD). Traditionally, it was believed that AD causes the BBB to become 'leaky,' allowing harmful substances to infiltrate the brain and potentially worsening the disease. However, the latest study suggests that the BBB remains largely resilient in a popular mouse model of AD.

Conducted by a collaborative team from the TTUHSC Department of Pharmaceutical Sciences and Brain Drug Discovery Center, along with the Graduate School of Biomedical Sciences, the research focused on evaluating BBB permeability in Tg2576 mice, a widely used animal model that develops amyloid plaques typical of AD. The team used a highly sensitive technique called liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with laser microdissection to precisely measure the leakage of [¹³C₁₂]sucrose, a molecule that normally cannot cross an intact BBB.

The findings revealed that sucrose levels in the brains of aged and young Tg2576 mice remained extremely low, indicating minimal to no leakage across the BBB. This was consistent across critical regions involved in cognition and memory, and even around amyloid plaques, the 'mortar' proteins that seal the BBB appeared to stay intact.

These results challenge the longstanding assumption of widespread BBB disruption in AD. Instead, they suggest that the barrier retains its protective functions despite the presence of amyloid plaques. This has important implications for drug delivery strategies, as therapies aimed at penetrating the BBB may need to consider that the barrier is not broadly compromised in this disease model.

While these findings provide valuable insights, researchers emphasize that additional models mimicking human physiology more closely are necessary. The next steps include studying the effects of FDA-approved monoclonal antibodies on BBB integrity, especially regarding microhemorrhages or brain swelling that could cause localized leakages.

Understanding the resilience of the BBB in AD could significantly influence future therapeutic approaches and drug design, ultimately aiming for more effective treatments that respect the barrier's protective role. The study underscores the complexity of AD and highlights the importance of refining our models to better understand disease mechanisms.

Source: https://medicalxpress.com/news/2025-09-blood-brain-barrier-resilient-widely.html