The LMD6 laser microdissection system was used to selectively isolate distinct areas inside the mind hemispheres of younger and aged Tg2576 AD mice following Amytracker 680 injection. Credit score: Fluids and Boundaries of the CNS (2025). DOI: 10.1186/s12987-025-00685-2
A staff of scientists at Texas Tech College Well being Sciences Heart (TTUHSC) has revealed new proof suggesting that the mind’s protecting protect—often known as the blood-brain barrier (BBB)—stays largely intact in a generally used mouse mannequin of Alzheimer’s illness. The invention challenges long-standing assumptions that Alzheimer’s illness causes the BBB to “leak,” probably reshaping how researchers take into consideration drug supply for the illness.
The examine, revealed July 23 in Fluids and Boundaries of the CNS, was carried out by a analysis staff from the Division of Pharmaceutical Sciences and the Mind Drug Discovery Heart at TTUHSC’s Jerry H. Hodge Faculty of Pharmacy in Amarillo, and from the TTUHSC Graduate Faculty of Biomedical Sciences. Ulrich Bickel, M.D., was principal investigator and senior writer, and Ehsan Nozohouri, a TTUHSC graduate analysis assistant, was lead writer. Co-authors embrace TTUHSC graduate researchers Behnam Noorani, Dhavalkumar Patel, Yeseul Ahn and Sumaih Zoubi.
Alzheimer’s illness is understood for reminiscence loss and cognitive decline. Within the mind, it’s marked by amyloid-beta plaques and tau tangles. For many years, scientists have additionally debated whether or not Alzheimer’s illness damages the BBB—the tightly linked endothelial cells lining the internal floor of mind blood vessels that act as a safety gate, blocking dangerous substances whereas letting in important vitamins by particular transporters.
“The BBB excludes 99% of large molecules, like proteins, and over 95% of smaller ones, including many drugs,” Nozohouri defined. “That’s why understanding whether it stays intact in Alzheimer’s is critical, especially for developing effective treatments.”
To discover this query, Nozohouri and colleagues used Tg2576 mice, a well-studied mannequin of Alzheimer’s illness that kinds amyloid plaques. The staff injected the mice with a innocent check molecule, [¹³C₁₂]sucrose, which usually crosses the BBB very poorly. Utilizing extremely delicate analytical instruments (liquid chromatography with tandem mass spectrometry, or LC-MS/MS) and superior tissue-sampling strategies (laser microdissection), they tracked whether or not sucrose leaked into totally different mind areas. Their key findings embrace:
No main leakage detected: Sucrose ranges within the mind remained extraordinarily low in each Alzheimer’s and wholesome management mice, each at younger and outdated ages, suggesting an intact barrier.
Secure throughout areas: Essential mind areas concerned in reminiscence and cognition confirmed no variations between teams.
Construction preserved: Even round amyloid plaques, tight junction proteins—the “mortar” sealing BBB cells collectively—remained principally unaffected.
Collectively, these outcomes point out that whereas small, localized modifications might happen close to plaques, the BBB as a complete retains its protecting operate on this mannequin.
“Our findings challenge the assumption of widespread BBB leakiness in Alzheimer’s disease,” Nozohouri mentioned. “This means that drug delivery strategies may need to be designed with the understanding that the barrier is not broadly compromised.”
A TTUHSC analysis staff revealed new proof suggesting that the blood-brain barrier (BBB) stays largely intact in a generally used mouse mannequin of Alzheimer’s illness. Ehsan Nozohouri, a TTUHSC graduate analysis assistant, was lead writer; Ulrich Bickel, M.D., (not pictured) was principal investigator and senior writer. Credit score: TTUHSC
Whereas the Tg2576 mouse mannequin gives invaluable insights, Nozohouri emphasised the necessity for added fashions that extra carefully replicate human physiology. There are medicine often known as monoclonal antibodies which were accredited by the FDA, they usually present some means to decelerate cognition decline.
As a subsequent step of their analysis, Nozohouri mentioned the staff may examine the rodent model of the accredited monoclonal antibodies to find out if there are any potential leakages brought on by microhemorrhages or mind swelling that probably may trigger the leakage on the blood-brain barrier.
“We still have much to learn about how Alzheimer’s disease impacts the brain’s defenses,” he mentioned. “Our ultimate goal is to better predict how drugs behave in patients, so we can design therapies that truly work.”
Extra data:
Ehsan Nozohouri et al, Assessing blood-brain barrier (BBB) integrity in an Alzheimer’s illness mouse mannequin: is the BBB globally or regionally disrupted?, Fluids and Boundaries of the CNS (2025). DOI: 10.1186/s12987-025-00685-2
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