The human brain has unique cognitive abilities compared to animals. However, it is also vulnerable to diseases that bring cognitive decline and neurodegeneration, such as Alzheimer’s. What makes the human brain so different? Neuroscientist Goriounova’s team thinks the answer lies in the function of neurons in our brains. Over the course of evolution, our neurons could have developed properties to process information faster and more efficiently in a larger brain, but which also made the neurons more vulnerable.
Neurons
Previously, Goriounova showed that the human brain holds specialized neuron types with distinct properties associated with IQ scores. These neurons could be crucial to human cognition because they are selectively lost in cognitive impairment. How these neurons function and form connections in the human brain is still unknown.
In her ERC proposal, Goriounova will test her prediction that cortical computation in the human brain depends on a highly interconnected network of these special types of neurons, which form fast and strong connections and can be fine-tuned by specific receptors to increase computational power.
Live brain tissue studies
These questions can only be investigated in adult living human neurons in their intact networks. This is extremely challenging because of the difficult access to human brain cells. Goriounova therefore collaborates with several hospitals in the Netherlands treating people with tumors or epilepsy. During surgical treatment, the neurosurgeon also removes a small piece of healthy cortical tissue to access the focus of the disease. This human brain tissue can be kept alive and used to study how neuronal cells function in their intact connections.
By collecting preoperative data from the same patients, the team can now link neuronal function to live brain network activity and cognitive scores of these patients. These methods make it possible to answer the question of the specialized function of human neurons relevant to cognition.
Consolidator Grant
The ERC uses the Consolidator Grant to support outstanding principal investigators for a period of five years at the career stage when they may still be setting up their own independent research team or program. Goriounova will receive €2 million for her project.
Alzheimer Nederland awarded €121,650 to Dr. Douglas Wightman (Complex Trait Genetics) to investigate genetic and environmental prediction of Alzheimer’s disease.
Alzheimer’s disease presents later in life but the biological processes that contribute to the disease development start well before symptom onset. Early prediction of Alzheimer’s disease risk before symptom onset would be beneficial in directing individuals to care earlier and may allow for more effective treatment.
In this project, Douglas will use machine learning methods to combine genetic risk and environmental risk to better predict Alzheimer’s disease. Models of genetic risk will be based on recent large genome wide association studies. There is a specific aim to create a minimal model that limits the number of features for easy clinical implementation.
This research aims to priortise genetic and environmental factors that can accurately
New research published in Cerebral Cortex https://academic.oup.com/cercor/article/35/8/bhaf127/8233140 reveals that many of the genetic changes that shaped the human brain and cognition, and even our vulnerability to mental illness, are surprisingly recent in evolutionary history.
The study, led by Ilan Libedinsky and Martijn van den Heuvel from the Complex Trait Genetics lab at CNCR, combined genomic dating methods with data from over 2,500 genome-wide association studies. This approach enabled the researchers to reconstruct evolutionary timelines for traits that cannot be studied through paleontological records, such as brain structure, cognition, and behavior, providing a genetic window into how humans have evolved over the past five million years.
Genes with these recent evolutionary modifications were linked to cortical structure, neuronal development, and intelligence. The same “young” genes were also highly expressed in brain regions involved in language, suggesting that evolutionary recent genetic modifications helped refine the neural circuits underlying complex cognition and communication, hallmarks of the human species. Some of these recent genetic changes were also associated with psychiatric disorders such as depression and schizophrenia.
By tracing when and where genetic variants emerged, the study opens new opportunities to investigate how evolutionary pressures on human-specific traits have shaped the molecular mechanisms underlying brain function and vulnerability.
The Scheper lab will follow-up on their previous work that established that GVB+ neurons are resilient to the tau-induced protein synthesis collapse and neurodegeneration, for which they identified key mechanistic components. Importantly, GVB+ neurons also retain the capacity to acutely induce the synthesis of plasticity factors in response to neuronal activity, showing the relevance of GVB-related resilience for neuronal function.
Supported by this Hersenstichting grant they aim to exploit the intrinsic resilience pathways that are activated in GVB+ neurons towards a therapy for tauopathies.
This 850.000 euro grant will allow him to expand his research team and gain fundamental new insights into the mechanisms and role of mRNA localization and local protein during the formation of synapses.
Each neuron in our brain forms thousands of synapses with other neurons that allows neuron communication. Each of these synapses requires hundreds of proteins that allow neurons to communicate with each other. While we now know which proteins are present in these synapses, it remains a great mystery how each neuron manages to bring these hundreds of proteins together in the right place and at the right time to form all these synapses. It is essential that we understand this because we know it goes wrong in neurological diseases.
In this project, his group will use innovative molecular techniques and live-cell and super-resolution imaging to study the role and mechanisms of mRNA localization and protein production in building new synapses at the right time and place. In addition, they will develop a new method to control these processes in neurons which would allow them to guide synapse formation.
New positions for a PhD student and postdoc will become available next year. For this, keep an eye on the team’s website: https://cncr.nl/research-team/neuronal_mrna_trafficking_and_local_translation/
More information on this VIDI project can be found at: https://vu.nl/en/news/2025/vidi-for-max-koppers-the-role-of-local-protein-production-in-synapse-formation
This community-driven data commons – built in collaboration with a broad network of (international) collaborators – integrates lipidomics from human and mouse brain tissue as well as induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, and microglia.
Using this resource, the authors show that iPSC-derived brain cell types display distinct lipid “fingerprints” that closely mirror those found in living tissue. One striking discovery is that the Alzheimer’s disease (AD) risk gene ApoE4 promotes cholesterol ester buildup specifically in astrocytes, a finding that aligns with lipid changes seen in human Alzheimer’s brain samples. Further analysis revealed that altered cholesterol metabolism in astrocytes directly affects immune-related pathways, including the immunoproteasome and antigen presentation systems. Strikingly these immune pathways were downregulated in the cholesterol ester accumulating ApoE4 astrocytes, challenging the view that the AD risk mutation ApoE4 increases glial reactivity and suggesting that immune responses may help protect against AD development.
By making these data openly accessible, the Neurolipid Atlas offers researchers an unprecedented platform to explore lipid dysregulation in brain disorders and accelerate discoveries into the molecular underpinnings of neurodegeneration.
The study is now published in Nature Metabolism and can be found here: https://www.nature.com/articles/s42255-025-01365-z
The mechanisms driving neurodegeneration in Parkinson’s remain incompletely understood, and disease-modifying therapies are still lacking. Although genetic forms of Parkinson’s are rare, they have provided crucial insights into disease mechanisms.
This project will be led by Dr. Ana Carreras Mascaro, who will investigate how specific genetic variants in Parkinson’s disease contribute to neurodegeneration in a physiologically relevant context. Building on Neurospector’s optimized human dopaminergic neuron cultures, she will develop new cell models to study early-onset, genetically driven Parkinson’s.
This research aims to uncover novel pathways involved in neurodegeneration and ultimately support the development of future therapeutic strategies.
Dr. Sanne Beerens (Memory Circuits team) will investigate how different intensities of aversive experiences alter synaptic properties of engram neurons in the prefrontal cortex. This could explain why traumatic memories in PTSD are so persistent while other fear memories fade.
Dr. Janina Kupke (Memory Circuits & Molecular Engram teams) will study whether DNA methylation, a lasting chemical mark on DNA, helps engram neurons maintain stable synaptic connections over time. Using advanced genetic tools and synapse-specific proteomics, she will map the protein landscape of engram synapses to reveal the molecular signatures that keep memories alive.
By revealing how engram neurons store and adapt memories, these projects aim to uncover new targets that may be new entry points for treatment of memory loss in Alzheimer’s disease, age-related cognitive decline, and the persistence of traumatic memories in PTSD.
Stressful experiences are generally remembered well, but such memories are often less precise, which results in memory generalization (recall of the stressful event when this is not relevant). This effect is mediated by stress-hormones. We will investigate how stress-hormones enhance memory generalization by studying the properties of the specific cells in the brain that store a memory, so-called engram cells. For this, we examine their specific cellular properties, their connections, and how we can reverse the effects of stress hormones to prevent memory generalization.
Neurons secrete chemical signal by two main principles: neurotransmitter release from synaptic vesicles (SVs) and neuropeptides from dense-core vesicles (DCVs). The presynaptic proteins RIM and MUNC13 play key roles in both pathways. However, it was still unclear how DCVs are targeted to release sites and whether RIM and MUNC13 are involved in this process. In the current study, Fiona Murphy and team show that three membrane-binding domains in RIM and MUNC13 regulate neuropeptide secretion and do so in a manner that is different from the way these same protein regulate neurotransmitter release.
Using neuropeptide secretion assays with single-vesicle resolution and peptidomics analysis of endogenous neuropeptide release in MUNC13/RIM null mutant neurons, the authors demonstrate that MUNC13 is essential for neuropeptide secretion. The N-terminus of RIM prevents MUNC13 degradation via the proteasome, and inhibiting proteasomal degradation partially restored neuropeptide secretion in RIM’s absence. RIM and MUNC13 both contain a C2 domain, a protein domain known to bind/recruit specific positively charged phospholipids in the plasma membrane (PIP2) that are known to be important for the membrane fusion reaction. The RIM C2 domain and the MUNC13 C1-C2B polybasic face are both essential for neurotransmitter release. However, the authors show that the two domains are redundant for neuropeptide secretion. In contrast, the lipid-binding MUNC13 C2C domain is essential.
This study shows that RIM and MUNC13 synergistically regulate neuropeptide secretion through membrane interactions and reveal new mechanistic differences between SV and DCV secretion principles.
The study was published in The Journal of Cell Biology and be found here: