Skip to main content

early-onset Alzheimer’s disease

This Is Why NIH Invests in Global Health Research

Posted on by Roger I. Glass, M.D., Ph.D., Fogarty International Center

Young girl getting immunized
Caption: Global partnerships fostered by NIH’s Fogarty International Center speed translation of scientific discoveries into lifesaving biomedical products. Credit: Gabe Bienczycki, PATH, Seattle

Efforts over the past few years to end the COVID-19 pandemic clearly reveal how global health impacts individual wellbeing and national security. At NIH, the Fogarty International Center helps the other institutes become engaged with global health research, which investigates the dual burden of infectious disease and non-communicable disease.

Global health research also encompasses data science, economics, genetics, climate change science, and many other disciplines. For more than 50 years, Fogarty has been building partnerships among institutions in the U.S. and abroad, while training the next generation of scientists focused on universal health needs.

America’s investment in Fogarty has paid rich dividends

During the pandemic, in particular, we’ve seen researchers trained by our programs make scientific discoveries that contributed to international security. Take Jessica Manning, a former Fogarty fellow who now conducts malaria research in Phnom Penh, Cambodia. Her team at the Ministry of Health sequenced the viral strain of SARS-CoV-2, the cause of COVID-19, infecting the first Cambodian patient and documented early the spread of this novel coronavirus outside of China.

Similarly, Christian Happi, director of the African Centre of Excellence for the Genomics of Infectious Disease, Ede, Nigeria, sequenced the first SARS-CoV-2 genome in Africa. Happi was able to do it by adapting the sequencing and analytical pipelines that he’d created back when he was a Fogarty grantee studying Ebola.

In Botswana, Sikhulile Moyo leveraged the skills he’d acquired while supported by a Fogarty HIV research training grant with Max Essex, Harvard School of Public Health, Cambridge, MA, to track COVID-19 mutations for his country’s Ministry of Health. Last November, he alerted the world of a new Omicron variant. Within six weeks, Omicron became the dominant global strain, challenging the ability of COVID vaccines to control its spread. In the Dominican Republic, William Duke, a national commission member, used what he’d learned as a Fogarty trainee to help create a national COVID-19 intervention plan to prevent and control the disease.

Fogarty’s fostering of global health leaders is one way we advance scientific expertise while ensuring our nation’s biosecurity. Another is by finding effective ways to study abroad the same health conditions that affect our own population.

Research conducted in Colombia, for example, may provide clues for preventing Alzheimer’s disease in the U.S. Fogarty support brought together neuroscientists Kenneth Kosik, University of California, Santa Barbara, and Francisco Lopera, University of Antioquia, Colombia, to study members of the largest-known family with an early-onset, rapidly progressive form of the disease. Over the years, Kosik and Lopera have trained local scientists, explored gene therapy targets, investigated biomarkers to monitor disease progression, and conducted drug trials in search of a cure for Alzheimer’s.

Researchers in other fields also discover unique opportunities to investigate populations with high rates of disease. Siana Nkya, a Fogarty grantee based in Tanzania, has devoted her career to studying the genetic determinants of sickle cell disease, which affects many people around the world, including in the U.S. We hope that US-African partnerships might develop improved, affordable treatments and a cure for all patients with this devastating disease. Similarly, people in the U.S. have access to state-of-the-art HIV treatment studies in places around the globe where incidence rates are higher.

Fogarty has supported many milestone achievements in HIV research over the years. Among them is a study that took place in nine countries. The research, led by Myron Cohen of the University of North Carolina at Chapel Hill, established that antiretroviral therapy can prevent sexual transmission of HIV-1 among couples in which one person is infected and the other is not. In fact, this research informs current HIV treatment recommendations worldwide, including in the U.S.

Americans will also undoubtedly benefit from projects funded by Fogarty’s Global Brain and Nervous System Disorders Research across the Lifespan program. For example, psychologist Tatiana Balachova, University of Oklahoma, Oklahoma City, has designed an intervention for women in Russia to prevent fetal alcohol spectrum disorders. In another project in South Africa, Sandra and Joseph Jacobson, Wayne State University, Detroit, conducted the first-ever prospective longitudinal study of the syndrome. Findings from both projects are ripe for translation within an American context.

Other examples of Global Brain program investigations with broad implications in our own country include studying early psychosis in China; capacity building for schizophrenia research in Macedonia; exploring family consequences from the Zika virus in Brazil; and studying dementia and related health and social challenges in Lebanon.

These are just a few examples of Fogarty’s work and its unique mission. What is most remarkable about Fogarty is that just under 90 percent of our grants are co-funded by at least one other NIH institute, center, or office. Collaboration, both within borders and across them, is Fogarty’s formula for success.

Links:

Fogarty International Center (NIH)

Overview of Brain Disorders: Research Across the Lifespan (Fogarty)

Former Fogarty Scholar Dr Jessica Manning Helps Cambodia Respond to COVID (Fogarty)

Christian Happi: Former Fogarty Grantee Leads COVID-19 Genomics Work in Africa (Fogarty)

Sikhulile Moyo: Fogarty Fellow Recognized for Omicron Discovery (Fogarty)

William Duke: Former Fogarty HIV Trainee Helps Lead Dominican Republic’s COVID Response (Fogarty)

Kenneth Kosic and Francisco Lopera: NIH Support Spurs Alzheimer’s Research in Colombia (Fogarty)

Former Fogarty fellow Siana Nkya Tackles Sickle Cell Disease in Tanzania (Fogarty)

Tatiana Balachova: Researchers Tackle Fetal Alcohol Syndrome in Russia (Fogarty)

Sandra and Joseph Jacobson: Fetal Alcohol Exposure Research Supported by NIAAA in South Africa, Ukraine and Russia Improves Prevention, Outcomes (Fogarty)

Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 22nd in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.


Largest-Ever Alzheimer’s Gene Study Brings New Answers

Posted on by Dr. Francis Collins

Alzheimer's Risk Genes

Predicting whether someone will get Alzheimer’s disease (AD) late in life, and how to use that information for prevention, has been an intense focus of biomedical research. The goal of this work is to learn not only about the genes involved in AD, but how they work together and with other complex biological, environmental, and lifestyle factors to drive this devastating neurological disease.

It’s good news to be able to report that an international team of researchers, partly funded by NIH, has made more progress in explaining the genetic component of AD. Their analysis, involving data from more than 35,000 individuals with late-onset AD, has identified variants in five new genes that put people at greater risk of AD [1]. It also points to molecular pathways involved in AD as possible avenues for prevention, and offers further confirmation of 20 other genes that had been implicated previously in AD.

The results of this largest-ever genomic study of AD suggests key roles for genes involved in the processing of beta-amyloid peptides, which form plaques in the brain recognized as an important early indicator of AD. They also offer the first evidence for a genetic link to proteins that bind tau, the protein responsible for telltale tangles in the AD brain that track closely with a person’s cognitive decline.

The new findings are the latest from the International Genomics of Alzheimer’s Project (IGAP) consortium, led by a large, collaborative team including Brian Kunkle and Margaret Pericak-Vance, University of Miami Miller School of Medicine, Miami, FL. The effort, spanning four consortia focused on AD in the United States and Europe, was launched in 2011 with the aim of discovering and mapping all the genes that contribute to AD.

An earlier IGAP study including about 25,500 people with late-onset AD identified 20 common gene variants that influence a person’s risk for developing AD late in life [2]. While that was terrific progress to be sure, the analysis also showed that those gene variants could explain only a third of the genetic component of AD. It was clear more genes with ties to AD were yet to be found.

So, in the study reported in Nature Genetics, the researchers expanded the search. While so-called genome-wide association studies (GWAS) are generally useful in identifying gene variants that turn up often in association with particular diseases or other traits, the ones that arise more rarely require much larger sample sizes to find.

To increase their odds of finding additional variants, the researchers analyzed genomic data for more than 94,000 individuals, including more than 35,000 with a diagnosis of late-onset AD and another 60,000 older people without AD. Their search led them to variants in five additional genes, named IQCK, ACE, ADAM10, ADAMTS1, and WWOX, associated with late-onset AD that hadn’t turned up in the previous study.

Further analysis of those genes supports a view of AD in which groups of genes work together to influence risk and disease progression. In addition to some genes influencing the processing of beta-amyloid peptides and accumulation of tau proteins, others appear to contribute to AD via certain aspects of the immune system and lipid metabolism.

Each of these newly discovered variants contributes only a small amount of increased risk, and therefore probably have limited value in predicting an average person’s risk of developing AD later in life. But they are invaluable when it comes to advancing our understanding of AD’s biological underpinnings and pointing the way to potentially new treatment approaches. For instance, these new data highlight intriguing similarities between early-onset and late-onset AD, suggesting that treatments developed for people with the early-onset form also might prove beneficial for people with the more common late-onset disease.

It’s worth noting that the new findings continue to suggest that the search is not yet over—many more as-yet undiscovered rare variants likely play a role in AD. The search for answers to AD and so many other complex health conditions—assisted through collaborative data sharing efforts such as this one—continues at an accelerating pace.

References:

[1] Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Kunkle BW, Grenier-Boley B, Sims R, Bis JC, et. al. Nat Genet. 2019 Mar;51(3):414-430.

[2] Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, DeStafano AL, Bis JC, et al. Nat Genet. 2013 Dec;45(12):1452-8.

Links:

Alzheimer’s Disease Genetics Fact Sheet (National Institute on Aging/NIH)

Genome-Wide Association Studies (NIH)

Margaret Pericak-Vance (University of Miami Health System, FL)

NIH Support: National Institute on Aging; National Heart, Lung, and Blood Institute; National Human Genome Research Institute; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Diabetes and Digestive and Kidney Disease; National Institute of Neurological Disorders and Stroke