Hypertension Drug May Help Treat Alzheimer's

By Jane Farrell

An FDA-approved drug thatΓÇÖs used to treat hypertension also reduces cell damage thatΓÇÖs often linked to AlzheimerΓÇÖs disease, a new study has found.

Researchers at Georgetown University Medical Center (GUMC) and the National Institutes of Health used laboratory neuronal cultures to reach that conclusion.

They say their work, published in the journal Alzheimer’s Research and Therapy, provides information supporting the potential effect of the drug candesartan ΓÇö as well as other Angiotensin receptor blockers (ARBs) for the early treatment of AlzheimerΓÇÖs disease.

“Our findings make sense in many ways,” says the study’s senior author Juan M. Saavedra, MD, from GUMC’s Department of Pharmacology and Physiology.  “Hypertension reduces blood flow throughout the body and brain and is a risk factor of Alzheimer’s disease. Previous epidemiological studies found that Alzheimer’s progression is delayed in hypertensive patients treated with ARBs.”

Using the neuronal cultures, the researchers explored the action of candesartan on the neurotoxic effects of exposure to excessive glutamate, a demonstrated injury factor in the early stages of AlzheimerΓÇÖs disease.

The scientists found that candesartan prevented glutamate-induced neuronal death. They conducted in-depth gene analyses of the laboratory results, demonstrating that candesartan prevented neuronal inflammation and many other pathological processes, including alterations in amyloid metabolism, a hallmark of AlzheimerΓÇÖs disease.

The studyΓÇÖs first author, Abdel G. Elkahloun, PhD, from the Comparative Genomics and Cancer Genetics Branch of the National Human Genome Research Institute, then compared gene expression in the neuronal cultures with published gene databases of autopsy samples from AlzheimerΓÇÖs disease patients. ΓÇ£The correlations were impressive ΓÇö the expression of 471 genes that were altered by excess glutamate in our cultures were also altered in brain autopsy samples from patients who suffered from AlzheimerΓÇÖs disease. Candesartan normalized expression of these genes in our cultures,ΓÇ¥ Elkahloun says.

ΓÇ£We hypothesize that candesartan, or other members of the ARB group, may not only slow progression of AlzheimerΓÇÖs but also prevent or delay its development,ΓÇ¥ Saavedra says.

The researchers say this work has immediate translational value, supporting testing candesartan, or other ARBs, in controlled clinical studies on patients at early stages of AlzheimerΓÇÖs disease.

Roman Hafko, PhD, formerly of the National Institute of Mental Health, also contributed to this work and is an author of the paper.