Previous research has suggested that controlling blood pressure may help lower the risk of developing Alzheimer’s disease. Now, in the search for effective therapies for the memory-stealing disease, scientists have shown evidence in the lab that an approved drug for high blood pressure may be able to reduce cell damage often linked to Alzheimer’s.
The findings, published online Jan. 28 in the journal Alzheimer's Research and Therapy, support the potential use of the drug candesartan--as well as other Angiotensin receptor blockers (ARBs)--for the early treatment of Alzheimer's disease.
"Our findings make sense in many ways," said senior author Dr. Juan Saavedra, of Georgetown University Medical Center, in a statement. "Hypertension reduces blood flow throughout the body and brain and is a risk factor of Alzheimer's disease.”
High blood pressure can wreak havoc on small blood vessels in the brain, including those that help with thinking and memory. So some scientists speculate that controlling blood pressure through medication may be able to lower Alzheimer’s risk. Previous studies have tied delayed Alzheimer’s progression in hypertensive patients to treatment with ARBs.
One of those studies appeared in the journal Neurology in 2013. Johns Hopkins researchers conducted an analysis of 3,000 elderly Americans and found that taking certain blood pressure medications was associated with a reduced risk of Alzheimer’s disease by at least 50%. The study found that ARBs, diuretics and angiotensin-converting enzyme ACE inhibitors were correlated with less risk of Alzheimer’s in people over the age of 75 with normal cognition. The investigators showed no similar relationship with beta blockers and calcium channel blockers, other types of blood pressure drugs. The same year, scientists published data showing that older people with high blood pressure, or hypertension, were more likely to have Alzheimer's biomarkers--indicators of disease--in their spinal fluid.
In this latest study, researchers used neurons grown in a laboratory setting to investigate whether candesartan, a type of ARB approved by the U.S. Food and Drug Administration, might have any effect on neurons showing signs of Alzheimer’s disease. When the drug was exposed to neurons with excessive glutamate, a trait that can speed up cell death in the early stages of Alzheimer's disease, the scientists found that candesartan prevented glutamate-induced neuronal death.
They then conducted in-depth gene analyses of these results and found that candesartan also prevented inflammation in neuron as well as other pathological processes, including the build-up of a protein called amyloid, long thought to be a main characteristic of Alzheimer’s disease.
Lastly, the researchers compared gene expression in the neuron cultures with published gene databases of post-mortem brain tissue samples from Alzheimer's disease patients. They showed that the expression of 471 genes that were altered by excess glutamate in the lab culture were also altered in brain samples from patients who suffered from Alzheimer's disease.
"We hypothesize that candesartan, or other members of the ARB group, may not only slow progression of Alzheimer's but also prevent or delay its development," Saavedra said.
Alzheimer’s has been a challenging area of study, and the field has seen unprecedented failures in drug development, so these types of very early-stage studies should be viewed with a skeptical eye. Of course, ARBs are a long way off from clinical trials in humans, but they have a better chance than new, investigational drugs do at getting tested in people since they’re already approved.
