When Cure Alzheimer’s Fund was created in late 2004, our mission was to end the disease by:
- Identifying all risk genes;
- Using those genes to reveal underlying disease mechanisms; and
- Aggressively pursuing potential therapies based on the knowledge gained from Alzheimer’s genes.
While we have not yet stopped the disease, we have come much closer to the goal line through substantial progress in these three key benchmarks.
What’s Next: Genes to Therapies
The ultimate goal of Genes to Therapies, our next major initiative, is the development of effective interventions at several points in the pathological cascade of Alzheimer’s disease.
Of the currently identified Alzheimer’s genes and candidate genes, more than 60 are being screened for mutations/functional variants in the Whole Genome Sequencing project. Of these, more than 20 variants currently are prioritized based on three important criteria for immediate and thorough investigation:
- High genetic impact or ranking in Alzheimer’s pathology;
- “Druggable,” as defined by being in known biological systems and producing proteins that appear to be most readily accessed and modified by typically successful therapeutic agents, such as small molecules or biologicals, e.g., antibodies; and
- Affect the most obvious intervention points, which include Abeta/plaque production and clearance, tangle formation/spreading and neuroinflammation.
Using our genetic discoveries as guideposts, Cure Alzheimer’s Fund has sponsored dozens of studies investigating the central mechanisms of action behind the Alzheimer's disease.
We also have a more thorough understanding of how Alzheimer’s pathology progresses from the earliest to latest stages of the disease. This model of Alzheimer’s allows us to identify three basic strategies for intervention in the process.
Foundations: The Alzheimer’s Genome Project™
Cure Alzheimer’s Fund has dedicated substantial resources to identifying the full complement of Alzheimer’s genes. The Alzheimer’s Genome Project™ was launched in 2005—and the first phase of this study led to the identification of more than 100 new Alzheimer’s candidate genes. This was the first large-scale, family-based study of the human genome specific to Alzheimer’s disease, and the first to report novel AD genes with statistical significance.
Additionally, a critical step was taken to identify not just which genes are associated with Alzheimer’s risk, but also all of the DNA variants and mutations in those genes that increase or decrease risk for late-onset Alzheimer’s disease. This was accomplished by Whole Genome Sequencing (WGS), which was used to read the entire genome of individuals with Alzheimer’s—all 3 billion base pairs of DNA across all 46 chromosomes. This allowed us to identify nearly 1,000 new genetic mutations in more than 50 different Alzheimer’s and frontotemporal lobar dementia genes, all of which functionally cause or protect against the disease. In identifying these new gene mutations, Dr. Rudolph Tanzi and his team effectively have identified the key biological causal agents that drive Alzheimer’s pathology in the brain.