Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterised by memory loss and dementia.
There are an estimated 18 million AD sufferers worldwide. The ageing populations of Europe and the U.S. make it likely that this number will increase dramatically in years to come.
Although the cause of AD is unknown, there are specific neuropathologies associated with it, most notably deposits (or plaques) of a fibrous protein called amyloid-beta.
Some researchers believe that amyloid-beta deposits are the cause of AD while others think they might be a consequence of the disease.
Research into AD has previously focused on the late stages of the disease. Although memory loss can occur prior to the development of AD, it can often be caused by other factors, making diagnosis difficult.
Now, researchers at the University of Minnesota, Minneapolis believe they have identified the earliest indication of AD. This may aid in the diagnosis of AD and perhaps slow or stop its progression.
The work, published in last week's Nature, involved the study of a strain of mice genetically engineered to synthesize a form of human amyloid-beta protein. These mice develop mild amnesia in middle age before the onset of severe AD symptoms.
Upon examination of the amyloid-beta extracted from the brains of the mice, Karen Ashe, who led the work, and her colleagues, discovered clusters consisting of 12 protein molecules, which differed from the plaques found later on in AD patients. The degree of memory loss in the mice was directly correlated to the number of amyloid-beta clusters found and, moreover, injecting the clusters into the brains of rats induced temporary amnesia.
Ashe suggests that the amyloid-beta clusters cause amnesia by preventing communication between neurons. Drugs which prevented this early clustering and also prevented amnesia in rats would provide good evidence for her her hypothesis.
It remains to be seen if patients in the early stages of AD do in fact have such amyloid-beta clusters in their brains. If they do, then finding the clusters in the blood would be an early warning sign that could help physicians diagnose the disease.
Other research, published in The Journal of Neuroscience last month, suggests that tetrahydracannabinol (THC), the active ingredient of marijuana, may slow the progress of Alzehimer's.
The research, led by Maria de Ceballos at the Cajal Institute and Complutense University in Madrid, first compared brain tissue of patients who had died of Alzheimer's with healthy pathients who had died at a similar age. It was found that there was dramatically reduced function of cannabinoid receptors CB1 and CB2, the proteins to which bind THC and other cannabinoids bind, in the tissue from Alzheimer's patients compared to healthy people.
Furthermore, the Madrid team found that cannabinoids reduced memory loss in rats, as measured by the animals' ability to find a hidden underwater platform. Rats injected with aggregated amyloid-beta protein and cannabinoids were better able to find the platform than rats injected with amyloid-beta and a control protein or two control proteins.
Microglail cells are known to activate the brain's immune response to the plaques of amyloid-beta found in AD and cause inflammation around the sites of plaque deposits. Maria de Ceballos and her team now confirm that cannabinoids counteract the activation of the microglial immune response via the actions of the CB1 and CB2 receptors, therefore reducing inflammation.
The team will now attempt to target the cannabinoid receptor that does not produce marijuana's psychotropic effects, in the hope of developing a therapy for Alzheimer's.