Amsterdam Neuroscience Annual Meeting 2019

Amsterdam Neuroscience Annual Meeting 2019


The registration for the 4th Annual Meeting of Amsterdam Neuroscience on 4 October 2019 in the Johan Cruijff ArenA is closed.

The Annual Meeting of 2019 has many elements that you may recognize from previous years. Highlights include the research reports and the pecha kucha talks during the morning session and the poster market during the lunch break. In the afternoon we will present a line-up of excellent speakers all around the same topic, i.e. on the genetics of brain disease. We want to celebrate our achievements and cordially invite you to join during our fourth Annual Meeting that is open to all generations, MSc and PhD students, postdocs, residents, principal investigators, educators and support staff.

Directors: Arjen Brussaard & Diederik van de Beek

Program of the Annual Meeting

(for abstracts of lectures and interviews see below)

08:30 Registration
09:30 Word of the directors Arjen Brussaard & Diederik van de Beek
09:45 Research Reports Hanneke Hulst - Cognitive rehabilitation in multiple sclerosis: is there a window of opportunity?
Judy Luigjes - Confidence estimation in compulsive disorders
Aniko Korosi - Early-life stress increases vulnerability to develop cognitive dysfunction: a focus on inflammation and nutrition
Henne Holstege - Cognitively healthy centenarians are genetically protected against aging associated diseases
10:45 Coffee break
11:15 Pecha Kucha By selected speakers from the nine research programs of Amsterdam Neuroscience
12:30 Poster market and lunch
14:00 Swammerdam lecture Steven Hyman (Harvard University, director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard)
Mental and neurological diseases: success in the genetics reveals great challenges for translational neurobiology and therapeutics
14:45 Interview with Steven Hyman By Matthijs Verhage (Amsterdam UMC, Location VUmc; CNCR department, Vrije Universiteit Amsterdam)
15:15 Research perspectives By Guus Smit, Danielle Posthuma & Ronald van Kesteren (CNCR department, Vrije Universiteit Amsterdam & Amsterdam UMC)
15:45 Interview with Jetske van der Schaar By Philip Scheltens (Amsterdam UMC, Location VUmc; Alzheimer Center Amsterdam)
16:15 Awards ceremony Awards for nine best posters and best Pecha Kucha presentation
16:30 Sponsored reception Drinks and Touch the grass

Research Report

Dr. Hanneke Hulst

Departments of Anatomy and Neurosciences, Amsterdam UMC & MS Center Amsterdam

Cognitive rehabilitation in multiple sclerosis: is there a window of opportunity?

Cognitive problems occur in up to 70% of the patients with
multiple sclerosis (MS) which are highly debilitating and an important cause of unemployment and disconnection from society. The first results of studies using non-pharmacological interventions to improve cognitive functioning in MS patients report mild to moderate effects. However, these effects might be confounded by the large heterogeneity of the patient population in terms of brain characteristics (lesion load, atrophy, brain network characteristics/disturbances;  i.e. not all patients might be able to benefit equally from such interventions and there may even be a limited window of opportunity). An essential step in the field of cognitive rehabilitation in MS is therefore the search for (neurobiological) markers that allow us to identify patients that will be responsive to cognitive rehabilitation. Ultimately, this will pave the way for personalized (cognitive) medicine in MS and perhaps even a shift from treatment towards secondary prevention.

Research Report

Dr. Judy Luigjes

Department of Psychiatry, Amsterdam UMC & University of Amsterdam

Confidence estimation in compulsive disorders

Compulsive behavior consists of repetitive self-defeating acts with devastating consequences. Obsessive-compulsive disorder (OCD) and gambling disorder (GD) are characterized by compulsive behaviour with both opposing (taking risk in GD; avoiding risk in OCD) and overlapping aspects (persistence despite devastating consequences). Interestingly, both disorders have been associated with an aberrant sense confidence albeit in an opposite direction: under-confidence in OCD and over-confidence in GD, which may explain both the shared and opposing characteristics of the behaviors. Recent studies suggest that confidence—an intuitive feeling about the probability of being correct—could be key in optimally adapting one’s behaviour. 

Using a decision making task where participants rate their
decision confidence we investigated whether and how confidence of OCD and GD patients deviates from each other and healthy controls Characterizingy the mechanisms of confidence in OCD and GD will elucidate mechanisms related to compulsivity and may lead to new avenues for treatment.

Research Report

Dr. Aniko Korosi

University of Amsterdam, Swammerdam Institute for Life Sciences | CNS division

Early-life stress increases vulnerability to develop cognitive dysfunction: a focus on inflammation and nutrition

Early-life stress (ES) is associated with increased vulnerability to cognitive impairments later in life. We investigate the role of a synergistic effect of stress, nutrition and the neuroimmune system in this early-life induced programming. We use a mouse model of chronic ES of limited nesting and bedding material during first postnatal week and study the brain structure and function under basal and challenged conditions (i.e. LPS, amyloid accumulation). Because of the key role of early nutrition during brain development we propose that an early dietary enriched with essential fatty acids might protect against ES-induced functional
deficits. We show that ES leads to cognitive impairments associated with
primed microglia with exaggerated response to LPS or amyloid accumulation. With an early dietary intervention with fatty acid we were able to prevent ES-induced cognitive decline mediated by modulation of microglia. These studies give new insights for the development of dietary interventions for vulnerable populations.

Research Report

Dr. Henne Holstege

Amsterdam UMC: Alzheimer Center and Department of Clinical
Genetics Delft University of Technology: Department of Intelligent Systems, Bioinformatics Lab

Cognitively healthy centenarians are genetically protected against aging associated diseases
Although the prevalence of dementia increases exponentially with age, some people reach ages well over 100 years enjoying great mental health. This indicates that cognitive decline is not inevitable.

To identify the molecular characteristics associated with resilience to cognitive decline we designed the 100-plus Study, an on-going prospective cohort study comprising cognitively healthy centenarians from a homogeneous Dutch population. Currently the cohort includes almost 370 cognitively healthy centenarians.

Preliminary findings indicated that siblings from the centenarians live on average 5-10 years longer compared to their birth cohort-peers. Also, the incidence of cognitive decline in siblings negligible, indicating a strongly heritable, overlapping etiology of retained cognitive health and longevity. Indeed, the genomes of centenarians are depleted with risk alleles associated with age related diseases such as dementia, cardiovascular diseases and diabetes. Moreover, the genomes of the centenarians are enriched with genetic variants that are protective against disease.

Specifically, exploring the effect of the protective heritable component is of value, as this discloses the molecular etiology underlying the delay or escape from age-associated cognitive decline. This may ultimately reveal an entry point for novel therapeutic targets that offer resilience to cognitive decline.

Swammerdam Lecture

Mental and neurological diseases: success in the genetics reveals great challenges for translational neurobiology and therapeutics

Prof. Dr. Steven E. Hyman

Director of the Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard, a core member of the Broad, and Harvard University Distinguished Service Professor of Stem Cell and Regenerative Biology.

Mental disorders represent a significant and growing public health problem worldwide, yet new treatment discovery has lagged other fields of medicine based on lack of insight into disease mechanisms.

This lack reflects the complexity of the human brain and its inaccessibility for direct study in life. Further, animal models have limited translational utility for mental disorders because of significant evolutionary divergence from humans in brain structure and function, especially in the cerebral cortex, and in such other features as regulatory genomic regions that play critical roles in brain development and risk of mental illness. This bleak picture is now changing as a result of rapid advances in computing, computational methods, and multiple relevant areas of technology. Since the beginning of this century we have gained powerful tools for genomics, cellular reprogramming, genome engineering, and investigation of neural circuit function and behavior. Large collaborative, unbiased genetic studies of mental disorders have yielded clues to pathogenesis that are being studied biologically in both human cellular models and animals.

Despite this progress, very significant challenges remain. Mental disorders are highly polygenic with overlapping patterns of genetic risk across
multiple disorders and healthy cognitive and behavioral phenotypes. In addition, no current experimental model systems, whether cellular or using living animals, fully serve the purpose of translation. Nonetheless, promising new approaches are coalescing in which human genetics poses disease relevant questions for basic neuroscience.

Translational hypotheses that emerge should, when possible, be tested in humans, human cellular models, or human samples. To illustrate, results from schizophrenia genetics implicate Complement Factor 4A (C4A) and many synaptic proteins in disease risk, suggesting the hypothesis that excessive synaptic pruning mediated by microglia during the typical adolescent period of onset represents a pathogenic mechanism. GWAS results for late onset Alzheimer’s disease (AD) indicates that more than half of common risk variants implicate microglia directly. As a result of these genetic findings in schizophrenia and late onset AD, new basic science efforts to characterize microglia are under way in animals, human postmortem tissue, and microglia derived from human induced pluripotent cells.

In both diseases (AD research is more advanced) fluid biomarker studies are investigating complement proteins, microglial proteins and synaptic
proteins. In parallel discoveries of common and rare DNA variants associated with schizophrenia have implicated many synaptic proteins, thus motivating new efforts to localize and characterize the functions of their proteins in both animals and human cellular models, as illustrated by the synaptic gene ontology project, SynGo. There is a long way to go before such discoveries lead to new effective therapies, but the last decade has seen real and durable progress in the neurobiology of once mysterious psychiatric disorders.

Interview with Steven Hyman

by Prof. dr. Matthijs Verhage, prof of Functional Neurogenomics, Center for Neurogenomics and
Cognitive Research, Vrije Universiteit Amsterdam & Amsterdam UMC - location VUmc

Research perspectives

New directions for science‐based intervention in brain disorders

by Prof. Dr. August Smit, professor of Molecular & Cellular
Neurobiology, head of department, CNCR, Vrije Universiteit Amsterdam

Neuroscience develops rapidly in various areas. Today’s perspective will cover two, Genetics and Alzheimer’s Disease, where conceptual breakthroughs are made at rapid pace. Guus Smit will be discussing
new developments in Genetics with Danielle Posthuma and novel views in Alzheimer’s disease research with Ronald van Kesteren.

by Prof. Dr. Danielle Posthuma, professor of Complex Trait Genetics,
CNCR, Vrije Universiteit Amsterdam & Amsterdam UMC

This exciting, booming field is providing extensive datasets frequently implicating hundreds of genes at the basis of a complex disorder.  Neuroscience has a hard time to use this reasure trove, thereby limiting the success in Genetics. A ‘Gravitation project' awarded by NWO is now aimed at radically changing the way we analyze complex raits. Danielle Posthuma, who coordinates this project, will explain this huge challenge and the potential it has.

by Dr. Ronald van Kesteren, associate professor Molecular & Cellular Neurobiology, CNCR, Vrije Universiteit Amsterdam & Amsterdam UMC

Alzheimer’s disease:
This active research field seems to renew itself over and over and new developments in understanding Alzheimers disease are at the horizon. Ronald van Kesteren will discuss the ‘new kid on the block’, by taking a new angle on the disease-affected neuronal circuitry. He will discuss how specific interventions were used to treat memory impairments in mice and how these might be translated to humans

Interview with Jetske van der Schaar

by Prof. Dr. Philip Scheltens, prof of Neurology and director of the Alzheimer Center Amsterdam, Amsterdam UMC

Jetske van der Schaar is a writer, entrepreneur, publicist and corporate speaker. She writes columns, articles and reviews and currently is working on her second novel. She also carries a rare gene variant of PSEN1, which is a cause of familial (dominantly inherited) Alzheimer’s disease (AD). This will inevitably lead to symptoms when she will be in her early fifties.

Van der Schaar’s grandfather, uncle and mother all died with early onset AD. In 2014 she consulted a clinical geneticist to get screened herself and got confirmation on her genetic status. In 2016 she came to the Alzheimer Center Amsterdam to know more about the disease and the possibilities to join research. One year later, on October 12, 2017, she was invited by Philip Scheltens to appear on national television (PAUW) and share her story. During the interview, she spoke for the first time about the disease and how it had affected her family and her own life. Since then she has become an ambassador for families with members suffering from dominantly inherited AD and a public figure both in the Netherlands and beyond.

In 2018 she featured as a major speaker during the international Dominant Inherited Alzheimer Network (DIAN) conference in Chicago, where scientists and DIAN family partners meet up at the DIAN-satellite meeting of the Alzheimer Association International Conference (AAIC). Jetske van der Schaar agreed to be interviewed by Philip Scheltens on stage during our Annual Meeting because she is passionate about the public debate on the disease and wants to be an active stakeholder in research as well. During the interview she will share her thoughts and insights on the taboo and stigma that surrounds this disease and how she thinks active participation of ‘patients’ will benefit research.