INDIANAPOLIS -- Indiana University School of Medicine scientists have received the university's largest single grant from the National Institutes of Health and will partner with a team of premier researchers around the country to lead a five-year national research study of a relatively rare form of Alzheimer's disease. Researchers hope the study will provide a foundation that may lead to new therapies for a disease that so far has resisted effective treatment.
The National Institute on Aging of the NIH has awarded IU a grant that is expected to total $44.7 million to fund the Longitudinal Early-onset Alzheimer's Disease Study. LEADS will follow participants diagnosed with early-onset Alzheimer's disease, which strikes people younger than 65 -- often in their 40s and 50s. The grant is in addition to a $7.6 million award last year that allowed planning and other start-up activity to begin for LEADS, bringing total federal support for the initiative to more than $52 million.
The study is led by IU School of Medicine neurologist and neuroscientist Dr. Liana Apostolova, who is partnering with Maria C. Carrillo of the Alzheimer's Association; Dr. Brad Dickerson of Massachusetts General Hospital and Harvard Medical School; and Dr. Gil Rabinovici of University of California San Francisco.
IU School of Medicine Dean Dr. Jay L. Hess announced the award at the IU Board of Trustees meeting in Indianapolis on Thursday.
"Alzheimer's disease is a complex and insidious illness that robs people of their memories and their dignity," IU President Michael A. McRobbie said. "With this extraordinary investment in research support from the National Institutes of Health, the LEADS project will marshal the extensive range of expertise and resources of IU's outstanding School of Medicine and those of our partners to help develop new therapies and transformative solutions for patients.
"We are very pleased that IU's Dr. Liana Apostolova will lead this extremely important national study of Alzheimer's disease in younger individuals, a subset of patients for whom the diagnosis is especially devastating, and congratulate her on this wonderful achievement. We are also grateful to the Lilly Endowment, whose original grant to support IU's Physician Scientist Initiative made it possible to recruit Dr. Apostolova in 2015."
An estimated 5.7 million Americans of all ages are living with Alzheimer's dementia in 2018. This includes an estimated 5.5 million people 65 and older and about 200,000 individuals younger than 65 who have early-onset Alzheimer's. Scientists hope that by studying Alzheimer's in this younger group, they can identify new potential paths to effective therapies for both early- and late-onset forms of the disease.
"We believe there is much to learn by studying Alzheimer's disease in this younger population of patients, who have been largely excluded from large-scale research studies of Alzheimer's disease," said Apostolova, the Barbara and Peer Baekgaard Professor of Alzheimer's Disease Research at IU School of Medicine.
Apostolova said the impact of the incurable disease on younger patients and their families is particularly devastating.
"Early-onset Alzheimer's impacts people who are often gainfully employed and raising families," Apostolova said. "The patients' spouses may have to quit working to take care of them, or the children may end up being responsible for taking care of their affected parent instead of going to college. It can be a disastrous situation for the family."
The LEADS program will enroll 400 early-onset Alzheimer's patients along with 100 healthy "control" participants. The early-onset participants will be patients with mild cognitive impairment or mild Alzheimer's and who have been found to have beta amyloid protein in the brain using PET scans, or positron emission topography. The buildup of the beta amyloid protein has been associated with the development of Alzheimer's.
The participants will undergo comprehensive examinations including cognitive tests, MRI and PET scans, collection of spinal fluid, DNA testing and more. They will be tested again in 12 months and in two years. PET imaging will be used to measure amyloid and tau, both major proteins associated with Alzheimers.
"The data and insights from research in this unique population are crucial to build our understanding of Alzheimer's, which is proving to be a very complex and challenging disease," said Dr. Eliezer Masliah, director of the Division of Neuroscience at National Institute on Aging. "Importantly, the methods used in LEADS will parallel other large Alzheimer's studies, so researchers can efficiently compare results to tease out clues on disease mechanisms."
"One possible result of this important and potentially groundbreaking research is that we come to understand with greater certainty whether early-onset and late-onset Alzheimer's are the same disease," Carrillo said. "If true, that means we can effectively conduct Alzheimer's clinical trials in people younger than 65. That would increase the pool of potential research volunteers. And these younger individuals generally have fewer age-related health conditions that add variability to a trial and often make the results harder to interpret."
LEADS represents an exceptional example of team science. Twenty institutions across the nation will participate in the patient recruitment and scientific analysis of the study. In addition to Apostolova, LEADS is led by three other co-principal investigators:
- Carrillo, who is chief science officer at the Alzheimer's Association. She and her team will oversee participant recruitment and retention efforts.
- Dickerson, who is the Tom Rickles Chair in Primary Progressive Aphasia Research at Massachusetts General Hospital and associate professor of neurology at Harvard Medical School. He will lead the magnetic resonance imaging core of the study and the clinical site at Massachusetts General Hospital.
- Rabinovici, who is the Edward Fein and Pearl Landrith Distinguished Professor in Memory and Aging at UC San Francisco and will oversee the PET core of the study and the clinical site at UC San Francisco.
Researchers will look for differences in clinical presentation, disease progression, levels of amyloid and tau and changes in brain gray matter between the early- and late-onset groups, and normal controls.
Although the early- and late-onset forms of Alzheimer's disease are believed to be fundamentally the same, there are differences on which LEADS will focus, Apostolova said. The early-onset form appears to act more aggressively and to progress faster. In addition, the initial symptoms among early-onset patients often differ from the memory decline that is the typical initial symptom of late-onset Alzheimer's disease, she said.
The clinical data and the biological specimens collected should enable scientists to discover additional genetic contributors to Alzheimer's development, as well as new clinical and cognitive outcome measures for use in Alzheimer's disease research, diagnosis and treatment, Apostolova said.
LEADS is funded by NIA grants numbered R56AG057195 and U01AG057195.
This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.