ACE Inhibitors and Alzheimer’s Prevention

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Cedars-Sinai scientists published a study in Journal of Clinical Investigation that suggests ACE inhibitors, in the right context and at the right time, can be a good thing.


Many people with high blood pressure take ACE inhibitors, medication meant to widen blood vessels by limiting activity of ACE (angiotensin-converting enzyme), a naturally occurring protein. However, this new research with laboratory mice bred to model AD shows that genetically targeting certain immune blood cells to overproduce the enzyme can systematically break down defective proteins in the brain associated with Alzheimer’s disease and cognitive decline.  The results demonstrate that ACE, not known for central nervous system involvement, can actually induce a protective immune response in the brain to ultimately affect cognition.  In addition, ACE could possibly have a novel role in the clearance of beta-amyloid from brain blood vessels.


Kenneth Bernstein, MD, engineered study mice to overexpress ACE in macrophages, microglia, and similar cells of the immune system.  The study shows the value of a strategy that delivers an enzyme to attack and destroy beta-amyloid to eschew resultant inflammation.  Scientists are yet to determine if the deposits result from overproduction of beta-amyloid or an inability of mechanisms, like the immune system, to clear the plaques.  Either way, a common view supports any strategy that reduces the amount of beta-amyloid protein in the brain as a way to delay progression of the disease.


Ultimately, mice with Alzheimer’s-like symptoms and those engineered to overexpress ACE in immune cells bred, and produced offspring with greatly reduced beta-amyloid protein levels, inflammation, and increased performance on learning and memory tests.


The research contemplates ACE as a natural enzyme that can be harmful or helpful, depending on how and where it is active.  Though it contributes to angiotensin II production, a hormone that causes high blood pressure, it can also quickly and efficiently lead an immune system response to beta-amyloid protein.



1)   Kenneth E. Bernstein, Yosef Koronyo, Brenda C. Salumbides, Julia Sheyn, Lindsey Pelissier, Dahabada H.J. Lopes, Kandarp H. Shah, Ellen A. Bernstein, Dieu-Trang Fuchs, Jeff J.-Y. Yu, Michael Pham, Keith L. Black, Xiao Z. Shen, Sebastien Fuchs, Maya Koronyo-Hamaoui. Angiotensin-converting enzyme overexpression in myelomonocytes prevents Alzheimer’s-like cognitive decline. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI66541

2)   Cedars-Sinai Medical Center. (2014, February 3). Can a protein controlling blood pressure enhance immune responses and prevent Alzheimer’s?. ScienceDaily. Retrieved February 6, 2014 from

By Emma Henson

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