Cholesterol drug shows benefit in animal study of Alzheimer鈥檚 disease
Improvement shown in blood vessel function following drug treatment
A cholesterol drug commonly prescribed to reduce cardiovascular disease risk restores blood vessel function in a mouse model of Alzheimer鈥檚 disease, according to a study in the April 4 issue of The Journal of Neuroscience. The drug simvastatin (Zocor庐) 鈥� which works by slowing cholesterol production 鈥� also improves learning and memory in adult, but not aged Alzheimer鈥檚 model mice. The findings add to a growing body of evidence that early treatment with statins protects against some of the symptoms of Alzheimer鈥檚 disease.
Alzheimer鈥檚 disease destroys nerve cells and compromises the function of blood vessels in the brain. Recent studies show people who begin taking statins as adults have reduced incidence of Alzheimer鈥檚 disease, while those who do not take them until they are older do not experience this benefit. While these studies point to the age-dependent benefits of statins, scientists continue to question how cholesterol treatment affects brain function in Alzheimer鈥檚 disease.
In a previous study, Edith Hamel, PhD, and colleagues at the Montreal Neurological Institute and Hospital 鈥� the Neuro, 91社区 University tested older Alzheimer鈥檚 model mice (age twelve months) that received a low dose of simvastatin for eight weeks. The drug helped improve blood vessel function, but did not boost memory in the older mice.
In the new study, Hamel鈥檚 group at the Neuro tested younger mice (age six months) and older mice (age twelve months) that received a higher dose of simvastatin for three to six months. While simvastatin restored brain blood vessel function in both groups, only the younger mice showed improvements in learning and memory tests. These younger mice also had higher levels of two memory-related proteins in the hippocampus 鈥� a brain region involved in learning and memory 鈥� compared with untreated mice.
鈥淭his study shows that simvastatin can protect against some of the damaging effects of Alzheimer鈥檚 disease on nerve cells involved in memory, if administered early in the disease process,鈥� said Hamel, the study鈥檚 senior author.
In people with Alzheimer鈥檚 disease, protein fragments called amyloid-beta (Abeta) form plaques between nerve cells that disrupt cell communication. Normally, these protein fragments are broken down and removed. In Alzheimer鈥檚 disease, the protein fragments clump together 鈥� a factor believed to contribute to memory loss. Hamel鈥檚 team measured the presence of Abeta proteins in younger and older Alzheimer鈥檚 model mice that received simvastatin. Despite the learning and memory improvements in younger mice, the drug did not reduce Abeta protein levels in either group.
鈥淭his article joins an increasing number of preclinical studies demonstrating that statins, in particular simvastatin 鈥� which easily penetrates the brain 鈥� can counteract aspects of Alzheimer鈥檚 disease, despite seeing no effects on amyloid-beta protein,鈥� said Ling Li, PhD, an Alzheimer鈥檚 expert from the University of Minnesota. 鈥淎lthough several clinical trials have yet to show the benefits of statins for Alzheimer鈥檚 disease, the key now is to figure out how to translate these exciting findings from bench to bedside,鈥� she added.
The research was supported by the Canadian Institutes of Health Research.
SOURCE: Society for Neuroscience
The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 40,000 basic scientists and clinicians who study the brain and nervous system. More information on Alzheimer鈥檚 disease can be found in the Society's Brain Briefings and Brain Research Success Stories publications.
The Montreal Neurological Institute and Hospital 鈥� The Neuro, is a unique academic medical centre dedicated to neuroscience. Founded in 1934 by the renowned Dr. Wilder Penfield, The Neuro is recognized internationally for integrating research, compassionate patient care and advanced training, all key to advances in science and medicine. The Neuro is a research and teaching institute of 91社区 and forms the basis for the Neuroscience Mission of the 91社区 Health Centre.聽 Neuro researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. The Montreal Neurological Institute was named as one of the Seven Centres of Excellence in Budget 2007, which provided the MNI with $15 million in funding to support its research and commercialization activities related to neurological disease and neuroscience.