New Evidence Shows Blood-brain Barrier Remains Intact In Alzheimer's Mouse Model

A squad of scientists astatine Texas Tech University Health Sciences Center (TTUHSC) has published caller grounds suggesting that nan brain's protective shield - known arsenic nan blood-brain obstruction (BBB) - remains mostly intact successful a commonly utilized rodent exemplary of Alzheimer's disease. The find challenges long-standing assumptions that Alzheimer's illness causes nan BBB to "leak," perchance reshaping really researchers deliberation astir supplier transportation for nan disease.

The study, published July 23 in Fluids and Barriers of nan CNS, was conducted by a investigation squad from nan Department of Pharmaceutical Sciences and nan Brain Drug Discovery Center astatine TTUHSC's Jerry H. Hodge School of Pharmacy successful Amarillo, and from nan TTUHSC Graduate School of Biomedical Sciences. Ulrich Bickel, M.D., was main interrogator and elder author, and Ehsan Nozohouri, a TTUHSC postgraduate investigation assistant, was lead author. Co-authors see TTUHSC postgraduate researchers Behnam Noorani, Dhavalkumar Patel, Yeseul Ahn and Sumaih Zoubi.

Alzheimer's illness is known for representation nonaccomplishment and cognitive decline. In nan brain, it is marked by amyloid-beta plaques and tau tangles. For decades, scientists person besides debated whether Alzheimer's illness damages nan BBB - nan tightly linked endothelial cells lining nan soul aboveground of encephalon humor vessels that enactment arsenic a information gate, blocking harmful substances while letting successful basal nutrients by circumstantial transporters.

The BBB excludes 99% of ample molecules, for illustration proteins, and complete 95% of smaller ones, including galore drugs. That's why knowing whether it stays intact successful Alzheimer's is critical, particularly for processing effective treatments."

Ehsan Nozohouri, a TTUHSC postgraduate investigation assistant, lead author

To research this question, Nozohouri and colleagues utilized Tg2576 mice, a well-studied exemplary of Alzheimer's illness that forms amyloid plaques. The squad injected nan mice pinch a harmless trial molecule, [¹³C₁₂]sucrose, which usually crosses nan BBB very poorly. Using highly delicate analytical devices (liquid chromatography pinch tandem wide spectrometry, aliases LC-MS/MS) and precocious tissue-sampling methods (laser microdissection), they tracked whether sucrose leaked into different encephalon regions. Their cardinal findings include:

• No awesome leakage detected: Sucrose levels successful nan encephalon remained highly debased successful some Alzheimer's and patient power mice, some astatine young and aged ages, suggesting an intact barrier.
• Stable crossed regions: Critical encephalon regions progressive successful representation and cognition showed nary differences betwixt groups.
• Structure preserved: Even astir amyloid plaques, tight junction proteins - nan "mortar" sealing BBB cells together - remained mostly unaffected.

Together, these results bespeak that while small, localized changes whitethorn hap adjacent plaques, nan BBB arsenic a full retains its protective usability successful this model.

"Our findings situation nan presumption of wide BBB leakiness successful Alzheimer's disease," Nozohouri said. "This intends that supplier transportation strategies whitethorn request to beryllium designed pinch nan knowing that nan obstruction is not broadly compromised."

While nan Tg2576 rodent exemplary provides valuable insights, Nozohouri emphasized nan request for further models that much intimately replicate quality physiology. There are drugs known arsenic monoclonal antibodies that person been approved by FDA, and they show immoderate expertise to slow down cognition decline.

As a adjacent measurement successful their research, Nozohouri said nan squad could study nan rodent type of nan approved monoclonal antibodies to find if location are immoderate imaginable leakages caused by microhemorrhages aliases encephalon swelling that perchance could origin nan leakage astatine nan humor encephalon barrier.

"We still person overmuch to study astir really Alzheimer's illness impacts nan brain's defenses," he said. "Our eventual extremity is to amended foretell really narcotics behave successful patients, truthful we tin creation therapies that genuinely work."