Meet Henne Holstege

Henne Holstege has spent her career exploring the genetics of neurodegenerative diseases and healthy aging. Her groundbreaking research on cognitively healthy centenarians has been instrumental in understanding how certain individuals defy age-related cognitive decline, potentially paving the way to new, protective approaches against Alzheimer’s and other age-related diseases. As of November 1st, Holstege joins the VIB-KU Leuven Center for Brain & Disease Research in Leuven to dive deeper into the molecular mechanisms that underlie aging.

Henne Holstege’s interest in healthy aging and cognitive decline was sparked by the remarkably healthy brain of Hendrikje van Andel-Schipper, who passed away at 115 years and 62 days old—making her the oldest Dutch person ever, a record that still holds today.

When she was 112, van Andel-Schipper called the neurology department of the University Medical Center in Groningen to let them know that while she had previously agreed to donate her body to science after she’d died, she was probably much too old now for it to be of any use.

Gert Holstege, Henne’s father and professor of Neuroanatomy at the Center, was responsible for bodies donated to science. He was intrigued by her call: someone at that age, preoccupied with those types of questions… He went to visit and examine van Andel-Schipper and found her (and her brain) to be in top shape. 

When she eventually passed away a few years later due to stomach cancer, her brain was donated to science. It turned out to be comparable to that of a typical 60-year-old, despite van Andel-Schipper being almost twice that age! 

What made van Andel-Schipper’s brain so uniquely resistant to the usual aging and disease processes that affect so many seniors? Henne Holstege just had to find out. She switched from studying breast cancer genetics to exploring the unique genetic features of people who grow extraordinarily old. 

Who is Henne Holstege?

Holstege has dedicated her career to unlocking the genetic factors contributing to healthy aging and neurodegenerative diseases. She heads the Genomics of Neurodegenerative Diseases and Aging section at the Department of Human Genetics at Amsterdam UMC and is a key member of the Amsterdam Alzheimer Center.

Holstege majored in biochemistry at the University of Leiden, after which she moved to Harvard Medical School in Boston to study the neurochemistry associated with satiety. Her academic journey took her back to the Netherlands, where she completed her PhD at the Netherlands Cancer Institute. Her early research focused on the genetic causes of breast cancer, giving her invaluable insight into how genetic mutations contribute to disease risk. During this time, Holstege became intrigued by a question that would later guide her research focus: Why do some families seem to escape common age-related diseases? This curiosity led her to neurogenetics and her research on healthy centenarians.

In 2010, Holstege joined Amsterdam UMC, where she established a new research section dedicated to identifying genetic and genomic factors associated with neurodegenerative diseases, including Alzheimer’s. Her research efforts and leadership in this field earned her the Alzheimer Research Prize in 2020 from the Hans und Ilse Breuer Foundation.

One hundred and healthy

One of Henne Holstege’s most influential research projects centers on understanding the genetic and lifestyle factors that allow some individuals to live over 100 years with minimal cognitive decline. She has established one of the world’s largest cohorts of cognitively healthy centenarians, creating a powerful resource for studying the unique genetic traits and mechanisms that protect against neurodegeneration.

Holstege: “By understanding the factors that enable some people to escape dementia, we can identify protective elements and, hopefully, translate those findings into therapies that benefit everyone.”

Holstege and her team are well on their way in their search for answers: “We’ve been able to show that centenarians are indeed genetically protected, and we’ve been able to pinpoint the genetic factors involved. Now, the next step is to understand the underlying mechanisms. That’s what I want to tackle in Leuven.” 

New opportunities

Holstege now plans to maintain her ongoing cohort studies in the Netherlands with a 50% appointment at UMC Amsterdam, and will spend the other half of her time in Leuven, where she will focus on advancing functional studies.

Holstege explains: “In Amsterdam, I’m running the 100+ study, which is now a well-oiled machine that continues to yield significant data. We’ve also built a comprehensive database for Alzheimer’s genetic research, the Alzheimer’s Genetics Hub, which enables GDPR-compliant data sharing—a crucial element for handling human data. We’ve now set up a sizable database specifically for this purpose, and I plan to integrate the 100+ data there. My aim in Leuven is to pursue large-scale omics data generation with the biomaterials from the centenarians, and to perform downstream functional experiments, further leveraging this rich data source."

Holstege is eager to maximize this new opportunity, noting, "We need to act fast with this data; the field is moving quickly. Leuven is an ideal setting for this work, and I’m excited to get started.”

Henne Holstege’s appointment in Leuven opens new opportunities for collaboration within the Center’s community and beyond. Through the resources offered by the Alzheimer’s Genetics Hub, she will be able to foster synergies not only within VIB, but also with UZ Leuven and the KU Leuven Neuropathology department, strengthening partnerships and expanding research efforts throughout Europe and the US.

VIB-KU Leuven Center for Brain & Disease director Patrik Verstreken: “With Henne joining our team, we gain a world-class researcher and a leader who brings a collaborative spirit and a wealth of knowledge in Alzheimer’s genetics. I am confident that her contributions will have a lasting impact on our center and on the field of neurodegenerative disease research.”

Connection and perseverance

Working with human material is essential to Holstege’s approach: “We’re not doing research to make mice better—we’re here to improve human health. Even with small amounts of human material, we can go a long way. We’re studying human samples, including from Alzheimer’s patients, centenarians, or population-based studies, to place these protective factors in context.” 

She shares how nice it is to be able to work directly with the community she aims to serve.

“Every year, we celebrate our progress with the centenarians in our cohort—it’s really a highlight of the year, connecting with the people behind our research. It adds a rewarding dimension to our work, really getting to know these incredible individuals we’re studying.”

Throughout her career, Henne Holstege has always followed where her interests and results led her, and today, that is Leuven. This attitude is also how she advises young researchers at the start of their career to approach science.

“I have never followed the rules and have always done exactly what I wanted. When Mrs. Van Andel passed away, I knew what I wanted to do and how I would do it. I've never let anything hold me back—so, my advice would be: believe in yourself and keep going."

Welcome to VIB, Henne!