Find all causes of Alzheimer's disease and a cure

In 2015, Cure Alzheimer’s Fund added new members to its Research Consortium and Scientific Advisory Boards, bringing substantially more depth to our research efforts while also maintaining our standards for funding research of the highest quality with the greatest potential impact on understanding and treating AD. Research funding went from $5.4 million in 2014 to $10 million, a nearly 90% increase.

As last year came to an end, we had a new paper accepted describing yet three new AD genes, all of which offer new targets for drug discovery, including one involved in cholesterol metabolism and two others that appear to be involved in tangle formation. We have also now finalized our whole genome sequencing data to arrive at roughly 350 different gene mutations and variants in about 50 genes that directly affect risk and/or age-at-onset for AD. Our growing database of detailed genomic data on AD continues to be the most comprehensive, largest, and of highest quality, worldwide. We are currently preparing the publication of our unprecedented whole genome sequencing data and plan to make all of it available to the research community.

The Genes to Therapies (G2T) initiative begun in 2014 accelerated in 2015.  The top Alzheimer’s disease genes, including the previously established four and a dozen new ones identified in Whole Genome Sequencing funded by Cure Alzheimer’s, are being studied for their mechanisms of action and as potential targets for therapies. The primary purpose of G2T is to translate our unprecedented database of novel genetic results into a deeper understanding of the causes of AD as well as novel drug discovery and development for treating and preventing AD.  Projects and scientists include Rudy Tanzi and the foundational genome project as well as CD33, APOE, ADAM10 and ATXN1; Li-Huei Tsai on ABCA7; Marc Diamond on MAPT; David Holtzman and Marco Colonna on TREM2; and nearly 20 others.

In addition to studying the above AD genes in various mouse and cell models, Cure Alzheimer’s Fund is also building on the success of the Alzheimer’s in a Dish technological breakthrough it funded to develop even more robust neuronal cell models for rapid drug screening. The 3-D Drug Discovery (3DDS) project with collaborators around the country is screening all existing approved drugs (~1200) and many clinically safe, but not yet approved investigational drugs to assess which can be can be repurposed to stop beta-amyloid deposition, tangle formation, and neuronal cell death in 3D cultures. The effort has already found several that appear to block tangle formation. In other studies, we are screening for drugs that will stop neuro-inflammation in AD using the AD genes involved in innate immunity in the brain, e.g., CD33. We are also developing novel 3-D systems to address innate immunity and the blood brain barrier (BBB) in AD.

Cure Alzheimer’s Fund has also supported many projects working on drug discovery and development efforts, understanding the role of neuroinflammation and innate immunity, and the role of the microbiome in mediating Alzheimer’s risk.  Two such compounds are entering clinical trials, one of which has proven to be so compelling that it received an NIH Breakthrough grant.  A number of projects are also examining ways to diagnose Alzheimer’s disease earlier and with more accurate biomarkers that track cognitive decline.