With its collaborators Genentech, Icelandic company DeCode Genetics has found a rare gene variant that marks protection against both Alzheimer's disease and general cognitive decline. This discovery could help researchers untangle the pathways and create better drugs. Alzheimer's affects 30 million people worldwide but there is no effective treatment.
The gene in question codes for the amyloid precursor protein (APP). This protein has a role in normal cells but sliced-off portions can create beta amyloid, which forms tangles and leads to plaques in the brains of people with Alzheimer's disease.
DeCode Genetics' research is underpinned by a unique resource--the company has exclusive access to the genetic data and health records of the Icelandic people, a geographically isolated group with low rates of migration and masses of genealogical data. The DeCode researchers screened whole genome sequence data from 1,795 Icelanders for low-frequency gene variants of the APP gene. Mutations are more commonly linked with increased likelihood of developing the disease, but this mutation was more common in the control group than in the people with the disease, suggesting that it could protect against Alzheimer's. The people with the mutation produced lower levels of amyloid beta, the harmful form of the protein, were more likely to live longer, and also had better cognitive function overall, compared with the general elderly population.
While the variant is too rare to serve as a diagnostic, it does act as a proof of principle for drug development in Alzheimer's disease. John Hardy of University College London, behind the discovery of the link between mutations in the APP gene and Alzheimer's, told Bio-IT World that: "it shows that long-term inhibition of BACE can prevent amyloid-driven disease," which has implications for other cognitive diseases including Down syndrome. A number of drug development programs, including some in clinical trials, target BACE1, an enzyme that cleaves APP to form beta amyloid.
DeCode Genetics emerged from Chapter 11 bankruptcy in January 2010, and has declared that it will remain close to its core competence, genetics, going forward.