Gift for genetic research largest-ever for Greater Indiana Chapter
Written by: Glenda Shaw
The Alzheimer’s Association Greater Indiana Chapter recently announced its grant to fund a $1 million genetic add-on to the Longitudinal Early-onset Alzheimer’s Disease Study (LEADS). The gift will support the work of Liana G. Apostolova, MD, Indiana University School of Medicine professor and principal investigator on the study, who aims to unlock the mystery of how Alzheimer’s disease develops in individuals under the age of 65.
Apostolova was first awarded $7.6 million from the National Institute on Aging in 2017, followed by a groundbreaking $44.7 million last year from the National Institutes of Health. The gift from the Alzheimer’s Association Greater Indiana Chapter will allow her to study the entire genome of all 600 LEADS participants across the country. She discussed how the new gift will impact the scope of her research.
The $1 million is the Indiana chapter’s largest-ever research investment. How did this gift to IU School of Medicine come about?
First, it’s very important to acknowledge that the Alzheimer’s Association is a huge partner in these activities. Maria Carrillo, who is the Chief Science Officer for the Alzheimer’s Association, is a co-principle investigator on the grant, so they have been extremely involved from the beginning.
The local chapter has acknowledged the importance of LEADS multiple times. We received the largest grant that the university or the state has ever gotten from the NIA, so it is obviously a very important study for many reasons and one that will have a global impact. With the encouragement by the central office of the Alzheimer’s Association to engage in direct local research support, the Indiana Chapter decided to donate $1 million from the chapter reserves to advance our research in a very fabulous and meritorious way. The $1 million will allow us to profoundly advance the genetics analyses of the study and this will undoubtedly translate in new Alzheimer’s disease genetic discoveries.
Early-onset affects about 200,000 Americans under the age of 65, according to the Alzheimer’s Association. What do you hope the genetic analysis of your 600 participants will reveal about this disease?
A lot of data has been collected from other studies on late onset Alzheimer’s and many genetic discoveries have already been made. Yet those combined explain only about 50 percent of the genetic underpinnings of this disease. What hasn’t been studied is the early onset population. This is a unique and very promising approach because the early onset patients have a much more aggressive disease manifesting in the young age at which they develop symptoms and the rapid rate of progression. The majority—95 percent—of Alzheimer’s cases develop symptoms in their 70s and 80s. Why are the early onset individuals getting symptoms so early, and why are the symptoms progressing so fast? We believe we are well set to uncover the answers to those questions if we explore their DNA.
What we’re doing in the project is very detailed clinical and cognitive evaluations, and a lot of biomarker collection, including MRI, amyloid, and PET scans, and blood for plasma and serum biomarkers, and DNA and RNA extraction. We’re also doing lumbar puncture for cerebral spinal fluid collection.
In the original NIA grant, what we have is whole exome sequencing, which is looking at the protein-coding regions of the human genome. The Alzheimer’s Association grant will now allow us to do whole genome sequencing, which is sequencing everything in the non-protein regions of the DNA and will enhance our likelihood for new discoveries
LEADS is being conducted at 20 institutions across the country. When will the new genetic phase begin?
We now have 20 institutions, but we are also adding additional sites, and that will bring the total to 24 before too long. Our clinical sites are poised to enroll 600 cognitively impaired and 100 control patients and follow them for 24 months with very detailed clinical and cognitive evaluations, and a lot of biomarker collection, including MRI, amyloid, tau PET scans, plasma, serum, DNA, RNA and cerebrospinal fluid collection. After this phase is over, the study will become a clinical trial network. We will then initiate clinical trials with investigational drugs.
Currently, we are still enrolling subjects and as soon as we have all 700 participants enrolled in the study with DNA collected we will start the analysis. We are set to fully enroll by October 2020.
Who makes up your IU team that will perform the genetic analysis?
This project will involve several other researchers from IU. The genetics experts who will be involved are Dr. Tatiana Foroud and Dr. Kelly Nudelman. The three of us are very excited about this project.
What are the goals for LEADS research in the next five years?
During these first five years of LEADS we will collect an enormous amount of data. The analyses that are currently funded are just scratching the surface of all the work that is possible. Many downstream and add-on analysis will spin off from this project. These will need to be supported by additional funding and resources for which we and many current and future collaborators will be applying in the coming years. Unraveling the potential for new discoveries of such a large data collection is not something a single institution can do on its own.
It’s a massive data collection and we will need the help of the scientific community to fund additional analyses and generate new discoveries and important findings that can advance the diagnosis, treatment, and cure for Alzheimer’s disease. The opportunities are indefinite.
We are also planning to move into the clinical trials domain in three to five years, where we will test important and promising novel therapeutic approaches in this unique population with such an aggressive form of this disease. We will find answers and we will find a cure. And we hope that LEADS will be instrumental in that role.
Read more about the $1 million gift from the Alzheimer’s Association Greater Indiana Chapter in our Newsroom.