This perspective article proposes a roadmap to interpret findings across different studies in validating retinal biomarkers for Alzheimer's disease.

This study, led by Prof. Bart De Strooper, discovered a mechanism by which neurons die in Alzheimer's disease. Read the news article (VIB)

In this paper, the Neuropixels team – including imec researchers – describe the protocol they developed to overcome major critical hurdles in using Neuropixels probes in the human brain in the operating room. Hopefully this information will guide future applications to gain general regulatory approval for use in humans.

This study found that serum GFAP, NfL and Aβ1-42/Aβ1-40 are valuable blood-based biomarkers for prognostics and monitoring in asymptomatic stages of Alzheimer’s disease.

This study applied imec's Neuropixels in the human brain to study auditory function.

This study on deep brain stimulation (DBS) in Parkinson’s disease found that evoked potentials, measured with EEG, can accurately predict clinical responses to the treatment. Future refinement of this approach may streamline DBS programming, thereby improving therapeutic outcomes.

This study, led by Prof. Patrik Verstreken, explores cell-type-specific α-synuclein and tau expression in human brain datasets and in fruit flies to determine which cellular environments react most to α-synuclein or tau toxicity.

Adequate deep sleep has an impact on the development of dementia. This pilot study in seven patients suggests that acoustic stimulation may help Alzheimer's patients improve their sleep.

This study showed the presence of phosphorylated tau pathology in the retina of the eye, which was associated with Alzheimer’s disease and inflammation.

This study evaluated a new biomarker method based on phosphorylated tau in blood plasma. The researchers concluded that plasma p-tau181 is an accurate tool to detect clinical as well as asymptomatic Alzheimer's disease.

This study shows that specific PET scans can track longitudinal changes in early Parkinson’s disease, but they may not correlate with clinical motor progression.

This publication describes the experimental method developed in the lab of Dr. Dries Braeken to deliver small molecules into cells via on-chip electroporation. This technique can be used for various biomedical applications, including mRNA transfection and gene editing.

In this correspondence, the authors looked at published databases on genome-wide association studies and polygenic risk scores to test for a potential correlation between Alzheimer’s disease and type 2 diabetes. They found no convincing genetic overlap between both conditions.

This study showed that minimally invasive epicranial current stimulation (ECS) is successful in suppressing tremor in rats, making it a promising neuromodulation method for patients with essential tremor.

This study led by Prof. Rik Vandenberghe found that specific polygenic risk scores are associated with amyloid accumulation in the asymptomatic phase of Alzheimer’s disease.

This meta-analysis looked at all published studies on DBS applied to AD and found inconsistencies and mixed results. Grouping the results from the few available studies together, DBS appeared to have no impact on the cognitive ability in patients with AD, but the authors conclude that further studies with larger sample sizes and randomized, double-blinded, sham-controlled designs are required.

This study investigated the contribution of pyroptosis, a mechanism of programmed cell death, to neurodegeneration in postmortem human brain tissue from Alzheimer’s patients. The results suggest that cell-type specific activation of pyroptosis is associated with neuronal loss in Alzheimer’s disease.

This study revealed a link between the length of amyloid fragments and the age at which symptoms first arise. The researchers hope we can use these insights not only to predict but eventually also to delay disease onset. (Read the VIB news article)

This study investigated the effects of continuous theta-burst stimulation (cTBS), a form of brain stimulation that is widely used in human neuroscience research, on single neurons in awake behaving monkeys.

This study led by Prof. De Strooper found increased functional connectivity and decreased calcium signaling in the human brain, several years before amyloid deposition. The results suggest that astrocytes mediate initial features of Alzheimer’s disease and drive clinical phenotypes.

In this large international study, investigators from the GENetic FTD Initiative found differential synaptic impairment, assessed by CSF biomarkers, in different genetic subgroups of FTD.

In this large international study, investigators from the Frontotemporal Dementia Prevention Initiative (FPI) modelled disease progression to facilitate planning of familial FTD clinical trials.

This study, led by KU Leuven researchers, investigated functional compensation processes in frontotemporal dementia, which may lead to a novel class of biomarkers with diagnostic and therapeutic implications.

This review paper discusses the relationship between phosphorylated tau and other Alzheimer’s disease-related proteins.

This study shows for the first time in vivo that synaptic loss regionally follows tau accumulation after two years, providing a disease-modifying window of opportunity for (combined) tau-targeting therapies.

In this correspondence, Liesbeth Aerts, Elsa Lauwers and Prof. Bart De Strooper highlight the need for an ambitious research agenda.

This review provides an overview of the current status of retinal imaging biomarkers of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Lewy body dementia, frontotemporal dementia, Huntington’s disease and multiple sclerosis.

This study led by Prof. Rik Vandenberghe investigated the prognostic value of cerebrospinal fluid-based biomarkers for cognitive decline. 228 patients of the Memory Clinic in Leuven participated.

This study investigated the propagation and specific subcellular localizations of tau pathology in donated brains from Alzheimer’s disease patients and healthy controls.

This commentary reflects the views of Prof. Bart De Strooper and colleagues on the controversial FDA approval of aducanumab

This article highlights the best strategies for polygenic profiling when assessing individuals for Alzheimer's risk

This review argues that disturbed synaptic proteostasis is an early driver of neurodegeneration in Parkinson's disease.

This international clinical study shows that cognitive motor training can improve cognitive functioning, mobility, and symptoms of depression in people with dementia. (read the news article)

In this personal view article, the authors discuss available evidence for human-to-human transmission of amyloid pathology, for instance via contaminated neurosurgical equipment. They found a possible link with cerebral amyloid angiopathy, but no proof that amyloid transmission can lead to Alzheimer's disease. Nevertheless, larger and long-term epidemiological studies are needed.

This review by the team of Prof. Ingeborg Stalmans highlights the clinical applications of a special type of retinal imaging, including promising first results for Alzheimer’s disease diagnosis.

This proof-of-concept study, led by Prof. Ingeborg Stalmans, demonstrates the potential of hyperspectral imaging of the eye to discriminate between Alzheimer’s patients and controls.

This study coordinated by Prof. Bart De Strooper and Dr. Mark Fiers investigated the link between Alzheimer’s risk genes and the two major disease hallmarks, amyloid-beta and tau pathology, in mouse models. The results show that the genetic risk for Alzheimer’s is reflected in the responses of microglia (the brain’s immune cells) to amyloid, rather than to tau. (read our news article)

In this study, the lab of Prof. Lieve Moons and Lies De Groef demonstrate the presence of soluble Aβ accumulation in the retina of young Alzheimer's mice, which later progresses to Aβ plaques.

This study investigated the brains of patients with mild cognitive impairment using a combined PET and MRI scan. They found that two brain changes are linked to cognitive decline: increased accumulation of a protein called tau, and a reduction in the number of synapses, the contact points between brain cells. The study suggests that both processes interact.

This review summarizes what is known about the role of astroglia in Alzheimer's disease. It also highlights recent findings from genetic and human stem cell studies, and discusses which future studies are needed to develop new targeted therapies.

A Belgian team of computational biologists led by Stein Aerts (VIB-KU Leuven) has developed a new bioinformatics method called cisTopic. cisTopic helps scientists to gain insight into the mechanisms underlying the differences in gene regulation across and within the cells in our body. (more information)

The research groups of Pierre Vanderhaeghen (VIB-KU Leuven) and Vincent Bonin (NERF) teamed up to investigate how human brain circuits form. They did this by transplanting human cells into a mouse brain. Check out the video abstract

There is increasing evidence that microglia play important roles in Alzheimer’s disease, and these supporting cells express many risk genes. In this technical study led by Prof. De Strooper, a new experimental mouse model is described in which human microglia have been transplanted. The mice express human genes associated with Alzheimer’s disease and will help to further elucidate the role of microglia in the disease process.

In January 2019, Dries Braeken attended the Organ-on-Chip In Development (ORCHID) Strategy workshop which intended to establish a European Organ-on-Chip roadmap. This resulted in six building blocks, which are detailed in this report.

The research groups of Joris de Wit and Bart De Strooper found a novel physiological role for the amyloid precursor protein (APP), the source of amyloid-β. The secreted part of APP interacts with the GABABR1a receptor, thereby modulating synaptic transmission, and offering a therapeutic target in Alzheimer’s disease. (more information)

In this study led by Peter Janssen, macaque monkeys received transcranial magnetic brain stimulation while they were performing a motor task, revealing insights in the effects of brain stimulation at the single-cell level.

The research group of Bart De Strooper investigated the microglia response to amyloid in a mouse model for Alzheimer’s disease. The response seemed to be influenced by the three main risk factors for the disease (aging, gender and genetics), suggesting that microglia are a potential therapeutic target. (more information)

A study led by Bart De Strooper discovered the physiological roles of PARL, a mitochondrial protein associated with Parkinson’s disease and diabetes. PARL deficiency in mice led to severe neurodegeneration due to aberrant mitochondrial structure and function. The new model is reminiscent of Leigh syndrome, and may help to shed light on mechanisms of neurodegeneration. (more information)

This review summarizes the current evidence for Parkinson-related protein changes in the retina and their potential as biomarkers.

A study at VIB-KU Leuven led by Philip Van Damme revealed neuroprotective effects of progranulin against TDP-43 accumulation and neurodegeneration in mice. The findings suggest that progranulin treatment holds potential for patients with frontotemporal dementia and ALS. (more information)

This review discusses the current strategies to make brain-on-chip devices, their role in the study of the healthy and diseased brain, and their limitations and future perspectives.

Researchers at imec have designed and fabricated a 16,384-electrode, 1,024-channel micro-electrode array (MEA) for high-throughput multi-modal cell interfacing. The chip offers intracellular and extracellular recording, voltage- and current-controlled stimulation, impedance monitoring and spectroscopy functionalities thereby packing the most cell-interfacing modalities on a single chip, and being the only one to enable multi-well assays. With this new chip, imec has created a platform that enables high quality data acquisition at increased throughput in cell-based cell studies. (Read more and watch the video)

A study led by Dr. Mark Fiers and Prof. Bart De Strooper detected microRNAs that are specifically upregulated in amyloid or tau transgenic mice, some of which are also altered in Alzheimer’s patients. (more information)

Based on emerging evidence, this review by the group of Prof. Patrik Verstreken proposes a model in which loss of synaptic homeostasis is central in Parkinson's disease.

The research group of Prof. Patrik Verstreken discovered why people with familial Parkinson’s disease often experience sleep problems. In transgenic fruit fly models and cells from patients, they detected dysfunctional processes in the cells responsible for sending signals to regulate sleep patterns, and managed to restore the defects. (more information)

Clinical practice relies on seizure diaries of patients to manage epilepsy, but less than half of all patients can accurately document their seizures. The development of algorithms that automatically detect seizure-related EEG changes and increases in heart rate can help to detect seizures in real-time and to generate an alarm signal for family members, caregivers, or health professionals. Smartphone-based wearable devices to measure several biosignals simultaneously, including EEG, will probably be available within the next 5 years.

Scientists at the ‘VIB-KU Leuven Center for Brain & Disease Research’ mapped a single-cell transcriptome catalogue of the entire adult fly brain sampled across its lifespan. These findings show an extensive heterogeneity in gene regulation that is linked to ageing and specific brain functions. Such insights generated from fly brain will serve as a reference for future studies of genetic variation and disease mutations.

KU Leuven and UZ Leuven scientists and clinicians aim to develop a wearable electroencephalogram (EEG) device that is small and unobtrusive enough to be used in daily life. They recorded epileptic EEG from behind the ear and found that it was a feasible approach to detect seizures in patients with focal epilepsy. Tools based on this technology provide valuable information for disease monitoring and management.

Researchers from the lab of Bart De Strooper (VIB/KU Leuven) successfully transplanted human neural cells into mouse brains containing amyloid plaques, one of the hallmarks of Alzheimer’s disease. Unlike mouse neurons, human neurons that developed in this environment were extremely susceptible to Alzheimer’s disease.

The teams led by Ludo Van Den Bosch (VIB/KU Leuven) and Catherine Verfaillie (KU Leuven) used stem cell technology to generate motor neurons from ALS patients carrying mutations in FUS. They found disturbed axonal transport in these motor neurons, but also identified genetic and pharmacological strategies that mitigate these defects in cells.

Engineers and scientists at imec, KU Leuven and VIB collaborated with researchers at HHMI’s Janelia Research Campus, the Allen Institute, and University College London (with grant funding from Gatsby and Wellcome) to build and test powerful new devices for detecting neural activity within the brains of living animals. The result is a silicon probe called Neuropixels, which can simultaneously record the activity of more than 200 individual neurons.

This study defines an integrator circuit for sleep homeostasis and provides a mechanism explaining the generation and persistence of sleep drive.

Imec does not only develop multi-electrode probes to probe brain activity, but also probes that can stimulate the activity of brain cells by shining light on them. Such probes can be used for ‘optogenetics’, a technique combining genetics and optics.