Two teams conducting parallel studies each found 2 genetic variants associated with Alzheimer’s disease, one of which was common to both studies. Philippe Amouyel’s team identified variants within CLU and CR1, while Julie Williams and her team also identified CLU and added PICALM to the mix. Combined, these 3 variants represent about 20% of the genetic risk relating to getting the disease.
In other words,
“If we were able to remove the detrimental effects of these genes through treatments, we could reduce the proportion of people developing Alzheimer’s by 20%,” Williams, of Cardiff University in Wales, told a press conference. “In the UK alone this would prevent just under 100,000 people developing the disease. So the significance of these results in truly meaningful.”
Alzheimer’s disease is the stuff of nightmares:
Although the course of Alzheimer’s disease is unique for every individual, there are many common symptoms. The earliest observable symptoms are often mistakenly thought to be ‘age-related’ concerns, or manifestations of stress. In the early stages, the most commonly recognised symptom is memory loss, such as difficulty in remembering recently learned facts. When a doctor or physician has been notified, and AD is suspected, the diagnosis is usually confirmed with behavioural assessments and cognitive tests, often followed by a brain scan if available. As the disease advances, symptoms include confusion, irritability and aggression, mood swings, language breakdown, long-term memory loss, and the general withdrawal of the sufferer as their senses decline. Gradually, bodily functions are lost, ultimately leading to death. Individual prognosis is difficult to assess, as the duration of the disease varies. AD develops for an indeterminate period of time before becoming fully apparent, and it can progress undiagnosed for years. The mean life expectancy following diagnosis is approximately seven years. Fewer than three percent of individuals live more than fourteen years after diagnosis.
The genomes of over 19,000 patients were analyzed, making the results statistically valid.
One of the new variants is in a gene active at synapses, the junctions between brain cells, and the two others help damp down inflammation in the brain. Inflammation is a known feature of Alzheimer’s, but it is often regarded as a consequence of the disease. Dr. Williams said that the detection of the new variants, which undercut the brain’s efforts to restrain inflammation, suggested inflammation might play a primary role.
It is not very often that scientists are prepared to stick their necks out and refer to research results as a “breakthrough”. This is one of those very rare occasions when it is a word that really does fit the bill. The importance of the discovery of three new genes with an association with Alzheimer’s disease in such a short space of time is significant.
Even before this latest development, clinical research was underway investigating different avenues for a cure.
As of 2008 there were more than 400 clinical trials under way to understand and treat Alzheimer’s disease. Over 100 of these studies were in the last phase before commercialization (phase three trials).
Many different investigation approaches coexist. Amyloid beta is a common target, existing many trials which aim to reduce it with different agents such as bapineuzumab, an antibody in phase III for patients in the mild to moderate stage, semagacestat, a γ-secretase inhibitor, MPC-7869, and acc-001, a vaccine to amyloid beta in phase II to be used in the mild stage. However, in a recent study an experimental vaccine was found to have cleared patients of amyloid plaques but did not have any significant effect on their dementia, casting doubt on the utility of such approaches.
Other approaches are neuroprotective agents, like AL-108 (phase II completed); or metal-protein interaction attenuation, as is the case of PBT2 (phase II completed). Finally, there are also many basic investigations trying to increase the knowledge on the origin and mechanisms of the disease that in the future may help to find new treatments.