Topic: Alzheimer's

Neurotrophins (NGF, BDNF, NT-3) are endogenous growth factors that exert neuroprotective effects by preventing neuronal death and promoting neurogenesis. They act by binding to their respective high-affinity, pro-survival receptors TrkA, TrkB or TrkC, as well as to p75NTR death receptor. While these molecules have been shown to significantly slow or prevent neurodegeneration, their reduced bioavailability and inability to penetrate the blood-brain-barrier limit their use as potential therapeutics. To bypass these limitations, our research team has developed and patented small-sized, lipophilic

Pluripotent cells, including embryonic stem (ES) and induced pluripotent stem (iPS) cells, are used to investigate the genetic and epigenetic underpinnings of human diseases such as Parkinson’s, Alzheimer’s, autism, and cancer. Mechanisms of somatic cell reprogramming to an embryonic pluripotent state are explored, utilizing patient-specific pluripotent cells to model and analyze neurodegenerative diseases.

Britta Engelhard’s research is devoted to understanding thefunction of the different brain barriers in regulating CNS immunesurveillance and how their impaired function contributes toneuroinflammatory diseases such as Multiple Sclerosis (MS) orAlzheimer’s disease (AD). Her laboratory combines expertise invascular biology, neuroimmunology and live cell imaging and hasdeveloped sophisticated in vitro and in vivo approaches to studyimmune cell interactions with the brain barriers in health andneuroinflammation.

Understanding and potentially reversing memory decline necessitates a comprehensive examination of memory's evolution throughout life. Traditional memory assessments, however, suffer from a lack of comparability across different age groups due to the diverse nature of the tests employed. Addressing this gap, our study introduces a novel, ACT-R model-based memory assessment designed to provide a consistent metric for evaluating memory function across a lifespan, from 5 to 85-year-olds. This approach allows for direct comparison across various tasks and materials tailored to specific age groups.

Dr. Pasinetti is the Saunders Family Chair and Professor of Neurology at Icahn School of medicine at Mount Sinai, New York. His studies allowed him to develop novel therapeutic approaches through investigation of preventable risk factors including mood disorders in the promotion of resilience against neurodegenerative disorder. In his presentation Dr. Pasinetti will discuss novel concepts about the gut-brain axis in mechanisms associated to peripheral adaptive immunity as therapeutic targets to mitigate the onset and the progression of Alzheimer’s disease and other form of dementia.

Fastball is a novel, fast, passive biomarker of cognitive function, that uses cheap, scalable electroencephalography (EEG) technology. It is sensitive to early dementia; language, education, effort and anxiety independent and can be used in any setting including patients’ homes. It can capture a range of cognitive functions including semantic memory, recognition memory, attention and visual function. We have shown that Fastball is sensitive to cognitive dysfunction in Alzheimer’s disease and Mild Cognitive Impairment, with data collected in patients’ homes using low-cost portable EEG. We are n

Coregraph is a tool under development that allows us to collect high-density data patterns during the administration of classic neuropsychological tests such as the Trail Making Test and Clock Drawing Test. These tests are widely used to evaluate cognitive function and screen for neurodegenerative disorders, but traditional methods of data collection only yield sparse information, such as test completion time or error types. By contrast, the high-density data collected with Coregraph may contribute to a better understanding of the cognitive processes involved in executing these tests. In addit

Genome-wide association studies and functional genomics studies have linked specific cell types, genes, and pathways to Alzheimer’s disease (AD) risk. In particular, AD risk alleles primarily affect the abundance or structure, and thus the activity, of genes expressed in macrophages, strongly implicating microglia (the brain-resident macrophages) in the etiology of AD. These genes converge on pathways (endocytosis/phagocytosis, cholesterol metabolism, and immune response) with critical roles in core macrophage functions such as efferocytosis. Here, we review these pathways, highlighting releva

The impact of apolipoprotein E ε4 (APOE4), the strongest genetic risk factor for Alzheimer’s disease (AD), on human brain cellular function remains unclear. Here, we investigated the effects of APOE4 on brain cell types derived from population and isogenic human induced pluripotent stem cells, post-mortem brain, and APOE targeted replacement mice. Population and isogenic models demonstrate that APOE4 local haplotype, rather than a single risk allele, contributes to risk. Global transcriptomic analyses reveal human-specific, APOE4-driven lipid metabolic dysregulation in astrocytes and microglia

Recent studies have begun to reveal critical roles for the brain’s professional phagocytes, microglia, and their receptors in the control of neurotoxic amyloid beta (Aβ) and myelin debris accumulation in neurodegenerative disease. However, the critical intracellular molecules that orchestrate neuroprotective functions of microglia remain poorly understood. In our studies, we find that targeted deletion of SYK in microglia leads to exacerbated Aβ deposition, aggravated neuropathology, and cognitive defects in the 5xFAD mouse model of Alzheimer’s disease (AD). Disruption of SYK signaling in this

This webinar will demonstrate changes that are already happening at individual, institutional and funder level to shift research culture toward supporting credible research, and will allow attendees working in neuroscience to ask further questions to our speakers. Our panel of speakers, chaired by Ana Dorrego-Rivas: Emily Farran, Professor in Developmental Psychology and Academic Lead Research Culture and Integrity at the University of Surrey Rosa Sancho, Head of Research at Alzheimer's Research UK Sepideh Keshavarzi, Senior Research Fellow at the Sainsbury Wellcome Centre

Cerebrovascular support is critical for healthy cognitive ageing. Reduced cerebral blood flow in ageing is caused, among other things, by hypertension, arteriosclerosis (i.e. stiffening of the arteries) and plaque formation. Arterial stiffness is predictive of cognitive decline, is a critical risk factor for cerebrovascular accidents, and has been linked to heightened risks for Alzheimer’s Disease and other forms of dementia. The elasticity of cerebral arteries is influenced by lifestyle factors, including cardiorespiratory fitness. Monica will discuss data obtained in their laboratory with ne

A diverse mix of neurotechnology talks and posters from researchers at Imperial and beyond. Visit our event page to find out more. The event is in-person but talk sessions will be broadcast via Teams.

Brain aging leads to cognitive decline and is the main risk factor for sporadic forms of neurodegenerative diseases including Alzheimer’s disease. While brain cell- and tissue-intrinsic factors are likely key determinants of the aging process recent studies document a remarkable susceptibility of the brain to circulatory factors. Thus, blood borne factors from young mice or humans are sufficient to slow aspects of brain aging and improve cognitive function in old mice and, vice versa, factors from old mice are detrimental for young mice and impair cognition. We found evidence that the cerebrov

Alterations in sleep are hallmarks of the ageing process and emerges as risk factors for Alzheimer’s disease (AD). While the fine-tuned coalescence of sleep microstructure elements may influence age-related cognitive trajectories, its association with AD-related processes is not fully established. We investigated whether sleep arousals and the coupling of spindles and slow waves, key elements of sleep microstructure, are associated with early amyloid-beta (Aβ) brain burden, hallmark of AD neuropathology, and cognitive change at 2 years in 100 late-midlife healthy individuals. We first found th

The overall aim of my research is to understand how the organisation of the synapse, with particular reference to the postsynaptic proteome (PSP) of excitatory synapses in the brain, informs the fundamental mechanisms of learning, memory and behaviour and how these mechanisms go awry in neurological dysfunction. The PSP indeed bears a remarkable burden of disease, with components being disrupted in disorders (synaptopathies) including schizophrenia, depression, autism and intellectual disability. Our work has been fundamental in revealing and then characterising the unprecedented complexity (>

WEBINAR 1 Breaking the barrier: Using focused ultrasound for the development of targeted therapies for brain tumours presented by Dr Ekaterina (Caty) Salimova, Monash Biomedical Imaging Glioblastoma multiforme (GBM) - brain cancer - is aggressive and difficult to treat as systemic therapies are hindered by the blood-brain barrier (BBB). Focused ultrasound (FUS) - a non-invasive technique that can induce targeted temporary disruption of the BBB – is a promising tool to improve GBM treatments. In this webinar, Dr Ekaterina Salimova will discuss the MRI-guided FUS modality at MBI and her research

The development of human induced pluripotent stem cells (iPSC) and their subsequent differentiation into neurons has provided new opportunities for the generation of physiologically-relevant, in vitro disease models. I will present our work using iPSC to modal familial Alzheimer's Disease (fAD) and Frontotemporal Dementia (FTD). We have investigated the mutation-specific effects of APP and PSEN1 mutations on Abeta generation in neurons generated from individuals with fAD, revealing distinct mechanisms that may contribute to clinical heterogeneity in disease. I will also discuss our work to und