Genomics of Neurodegenerative Diseases and Aging (100-plus Study)

Department of Human Genetics, Amsterdam UMC.

Our research

An estimated 60-80% of the chance to develop Alzheimer’s disease depends on genetic factors, and similar percentages apply to other neurodegenerative diseases. Thousands of genetic risk factors are involved: some occur only very rarely in the population, others are more common. Each individual is uniquely vulnerable for developing diseases, which depends on the unique constellation of disease associated genetic variants they inherited from their parents. 

Therefore, it is important to know which genetic factors are involved: (1) they point towards the molecular processes underlying the disease, necessary to design accurate treatment strategies. (2) they can be used to predict the individual vulnerability for diseases, far before the onset of symptoms. In the future, when treatment options become available, predicting who is at risk before the onset of symptoms will allow timely and accurate treatment. 

Unfortunately, only a fraction of disease associated genetic elements is currently known. To identify novel genetic elements, our group compares the genetic constellations of those affected by neurodegenerative diseases with cognitively healthy individuals. Next to identifying risk-increasing genetic variants, our group takes a unique approach: we aim to identify genetic elements that protect against neurodegenerative diseases. 

We conceived the 100-plus Study: an on-going prospective cohort study of centenarians who self-reported to be cognitively healthy, their first-degree family members and their respective partners. By investigating the genetic constellations and biomaterials of those who escaped disease until extreme ages, we aim to learn how cognitive decline can be avoided. 

Ultimately we hope that our findings will contribute in helping others achieve the same: reaching extreme ages without dementia. Read more about the 100-plus Study.

In our aim to translate our scientific findings directly to the clinic, our research section forms the bridge between the department of Human Genetics and the Alzheimer Center Amsterdam.   

Dr. Henne Holstege, section leader & PI of the 100-plus Study, amidst several centenarians at the 100-plus day 2019. To read an interview with Dr. Henne Holstege click here.

About our centenarians

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Centenarians participated

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Partners participated

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Siblings participated

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Partners of siblings participated

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Partners of children participated

The team

Join the lab

Currently, there are no open positions. Interested in an internship? Please mail w.l.m.stoker@amsterdamumc.nl for possiblities.

Data sharing and the Alzheimer Genetics Hub

We are open to collaborations and data sharing. Please contact us at info@holstegelab.eu.

One of our projects is the Alzheimer Genetics Hub: http://www.alzheimergenetics.org. This secure platform allows for data sharing of privacy-sensitive data: genetics data or other large scale data with strong privacy requirements. Please contact us for additional information. 

Announcements

Agenda

April 10 2026
TN2 Symposium 2026

Join us at TN2, where researchers from both basic science and clinical practice come together in the field of Translational Neuroscience, fostering collaboration between Dutch experts and their international colleagues. At the upcoming TN2 Symposium, Henne Holstege will present an engaging keynote on Pathways to Cognitive Resilience in Extreme Longevity. Simply click the link below and fill out the form to attend this symposium at the RDC-Adore building. We look forward to seeing you there!

Registration form TN2 Symposium 2026 

May 11-13 2026
Holstege Lab Retreat

From May 11th to the 13th, the Holstege research team will go on a retreat together. It will be a retrospective and prospective moment, contemplating the successes within the research team over the last year, and looking forward to what is coming up!

 

May 14 2026
MIA-Portugal Ageing Spring School 2026

On the 14th of May, Henne Holstege will give a talk at the MIA Portugal Ageing Spring school, which is a 3-day international gathering that brings together upcoming and established scientists within ageing research. Here, she will present on the 100-plus Study, including which factors play a part in cognitive resilience in extreme longevity.

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