The start
There are several reasons in neuroscience to conduct research on human brain tissue. First, there are situations that cannot be studied in animals, such as the molecular basis of gender identity—the feeling of being male or female
1, or the molecular alterations in suicide
2. Second, it is necessary to validate findings from animal models for brain disorders in the human brain
3. Animal experimental models often fail to predict what happens in the human brain.
In the 1970s, animal experiments suggested that vasopressin was a ‘memory hormone’ while oxytocin was a ‘forgetting hormone’. My lab had just developed techniques to specifically demonstrate these neuropeptides under the microscope in the rodent and human brain
4,
5. In addition, it became clear at that time that Alzheimer’s disease would become the epidemic of the future. It was therefore obvious to examine changes in vasopressin and oxytocin in the brains of Alzheimer’s patients. However, how to obtain such brain material? It took me four years in the late 1970s to obtain five clinically well-documented brains of Alzheimer’s patients for research, even though there were already 100,000 patients with this brain disorder in the Netherlands. Collection of such brains was very difficult because these patients did not die in an academic hospital, but at home or in a nursing home where there was no research tradition. To conduct serious research on the human brain, it was therefore necessary to establish an infrastructure with donors who consented to a brain autopsy and the use of the tissue and clinical data for research. Such an infrastructure should also contain an autopsy room and people who could dissect the fresh, soft brain structures according to anatomical borders and make neuropathological diagnoses of the brain material. In addition, it should contain administrative staff who speak to and manages the donors, and handle the distribution of tissue to researchers and match the controls for many possible confounders. Since I only needed 3% of each brain for my own research, the rest could be made available to other researchers by open access. We called this infrastructure the Netherlands Brain Bank (NBB). Ultimately, the first research project revealed that the vasopressin and oxytocin cells were highly active and fully resilient amidst the Alzheimer’s changes in the brain. Disappointing? No, because it was also the beginning of the realization that highly active cells were resistant to the disease process, which I paraphrased as ‘use it or lose it’
6, and is still a focus in our research interest.
Collaboration with the Free University in Amsterdam
Prof. Frans Stam was, at the time, the only person in the Netherlands interested in the brains of Alzheimer’s patients. He was a neurologist, psychiatrist, and neuropathologist. I had knew him since the first lecture I gave on this disease. I explained that all the brain changes described in Alzheimer’s were also present in ‘normal aging’, although in the latter they were less pronounced and occurred at an older age. Age is also the main risk factor for Alzheimer’s disease. Therefore, I concluded that Alzheimer’s seemed to be an accelerated, premature form of aging of the brain. Afterwards, Prof. Stam came to me rather agitated and said, ‘I have spent my whole life trying to convince people that Alzheimer’s is a brain disease, and now you are telling me it’s just aging!’ I replied, ‘If it is an accelerated, premature, and therefore abnormal form of aging, it is abnormal aging and thus a disease, isn’t it?’ I still think the same way about the Alzheimer process. At one point, I told him about my plan to start a brain bank. Prof. Stam was always a bit grumpy. He grumbled that a brain bank was all nonsense and unnecessary, but that if that’s what I wanted, I could use his autopsy room at the Free University. And that is why the NBB still performs the autopsies at the Free University until today.
Autopsies
The time between death and obtaining brain tissue must be as short as possible, because then the chemistry may best reflect what it was during life. So, from the beginning, we had a 24/7 duty schedule. My PhD students and postdocs working on human brain tissue and my technicians helped on the autopsy team. For example, Eric Fliers, Bart Fisser, Unga Unmehopa, and Rivka Ravid were involved with the Brain Bank early on. I myself also performed the autopsies at night, alternating with neuropathologist Wouter Kamphorst. He said he himself did not want to donate his brain to the NBB, because he did not want me to see how small his brain was and how large his cerebral ventricles were. However, Wouter Kamphorst was indispensable in establishing the NBB. A neuropathologist in training, Annemieke Rozemuller, who would later become a professor and ultimately perform all neuropathological diagnoses for the NBB, also joined us. Those night shifts were not easy, because I had to work again the next morning as director of the Netherlands Institute for Brain Research and as team leader of my research group ‘Neuropsychiatric Disorders’.
Pioneering period
Many challenges had to be overcome. We obtained donors through newspaper interviews, television appearances, lectures in nursing homes for families of Alzheimer patients, and so on. Although the NBB was established to study Alzheimer’s disease, from the outset we wanted to expand our scope to include a wide range of neurological and psychiatric diseases. Brain tissue was also made available to a growing number of other national and international research groups from the outset, and open access remains a top priority at the NBB, as one of the few brain banks in the world.
Control material was also initially unavailable, because no one saw any reason to perform a brain autopsy on patients who did not have any brain disease. However, in research on brain diseases, every piece of brain tissue from someone with a brain disease must be compared with the exactly same piece of brain tissue from someone without a brain disorder of the same age, gender, time after death, time of day, season of death, and so on, since all these factors are accompanied by molecular differences in the brain. In addition, there are genetic factors, the medications used, and the way the person died etc., all of which also have a significant impact on the research findings. All this means that a well-running brain bank essentially needs about five times more control samples than samples from patients with a brain disease in order to get the right match. An additional reason for the importance of older, ‘healthy’ control donors is that we can study the very first changes in age-related diseases like Alzheimer’s and Parkinson’s in the brains of these people, which are only visible under a microscope but have not yet caused any symptoms. If we live long enough, we will all have such early signs of a brain disease.
As mentioned above, for a proper research, the time between death and the acquisition of brain tissue must be as short as possible. This is only possible when donors and their families complete all the paperwork in advance and know exactly what will happen after death. The funeral director also has to understand the importance of urgency. I received several calls at night from the police, who could not understand why the funeral director, driving at high speed, was saying he had to rush the deceased to the hospital. But later, a motorcycle officer even escorted a funeral director who was stuck in rush hour traffic onto the shoulder.
Donors
Of the more than 5,300 registered donors, some are deeply involved and asked other patients to sign up as donors. They were excellent ambassadors for the NBB. Others wanted to know more about their brain disease. I once received a call from a donor with multiple sclerosis (MS), who exclaimed, "I want to see the enemy." We then placed a microscope on the table of his wheelchair at the institute, and Inge Huitinga examined brain slices from MS patients with him. Other donors asked us the most surprising questions. We were able to reassure a donor who asked if we wanted to wait with the autopsy until her aura had disappeared: we have never performed an autopsy on anyone whose aura was still visible, I told her. In 1990, we took the initiative to recruit MS donors as well. We subsequently had to face a legal challenge. We were sued by the husband of an MS patient. He believed MS was not a brain disease, but a muscle disease. ‘Surely my wife isn’t crazy?’ was his argument. Fortunately, the judge did not accept his misconceptions. For myself, personally, it is a great comfort that whatever stupid things I say or do now, my brain will be put to good use by the Netherlands Brain Bank later.
The NBB today
Prof. Inge Huitinga, my successor as director of the NBB, has built it into a highly professional organization with 32 employees. Today, the NBB is a financially sound, internationally recognized Brain Bank, a global leader in open access, clinical documentation, and ethical aspects
7. Neuropathology has become better than anywhere else under Prof. Annemieke Rozemuller. This has made the NBB an international benchmark, and thus for example the model in all aspects for the network of brain banks we are helping and supporting to establish in China
8. Staff of the Chinese Brain Banks have been trained by the staff and neuropathologists of the NBB and follow all NBB procedures. In its forty years of existence, the NBB has consistently held more than 5,000 donors, performed more than 5,000 rapid autopsies, and provided more than half a million samples of clinically and neuropathologically well-documented brain tissue to over 1,800 research projects in 25 countries. When it became known that brain tissue from the NBB was being sent around the world, we received a call from a donor. She had a severe fear of flying and did not want her brain samples to be flown to other parts of the world later, so she withdrew as a donor. The NBB material has resulted in 3,200 scientific publications in international journals, and Inge Huitinga, through the NBB, has secured several very large research grants. The NBB has become a strong, young adult in her forties.
Visit Queen Maxima
On September 18, 2025, the NBB commemorate its 40th anniversary in the presence of Queen Maxima of the Netherlands (Figure 1). This was actually the second time Maxima visited the NBB. The previous visit was much less official, as she arrived as a princess in 2008. This time, it was a strictly protocol-driven event where every minute had to be documented and approved in advance by her staff. Maxima, however, turned it into a spontaneous gathering that was met with much interest and laughter. Upon entering our lecture hall, Maxima broke with the protocol, shook my hand, and said, ‘Hello Mr. Swaab, how are you?’ I welcomed her. The second ‘Dick Swaab Prize’ was awarded for outstanding research on human brain material from the NBB to Giorgia Tosoni (Paper submitted). She demonstrated new brain cells in the hippocampus of people who were resistant to Alzheimer’s disease. Giorgia received her PhD with honors under the supervision of our PI Evgenia Salta, a research leader at the Brain Institute. There were compelling interviews with NBB donors who had psychiatric problems, and with two psychiatrists who explained to Maxima that, due to a lack of knowledge, they had to use trial and error to find the right therapy for each patient. This underscored the importance for the NBB of focusing research on brain material from psychiatric patients over the next 10 years in order to find new therapeutic targets and develop better, personalized therapies. Maxima visited a few laboratories, where Dr. Lin Zhang, who is working in my group, gave also a short presentation. Lin, a Chinese forensic pathologist, who defended her PhD thesis in Amsterdam with honors, explained that her research on suicide and euthanasia revealed brain changes that seemed to be related to the desire to die, that were different from those seen in depression. This may hopefully lead to new targets for anti-suicide drugs. This prompted Maxima, in a later roundtable discussion, to spontaneously mention her sister, who had untreated psychiatric problems in Argentina and had committed suicide (Figure 2). It was clear how deeply this still affected her. The large press presence generated numerous newspaper articles and radio and television coverage. This immediately resulted in more than five-hundred applications for papers by potential new NBB donors, achieving a key goal of the meeting.
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