UKDRI Connectome Poster Series Highlights

Our @ukdementiaresearchinstitute Connectome Poster in a Short series concludes with a poster from Shikha Kataria at UKDRI Cardiff. Her work investigates how electrophysiological dysfunction in LRRK2 Parkinsonian neurons relates to disruption in the autophagy lysosomal pathway, a process that is essential for clearing damaged proteins and maintaining neuronal health.

Using iPSC derived cortical neurons, Shikha compares wild type and LRRK2 mutant cell lines through a combination of multi electrode array recordings, imaging based assessments and autophagy markers. The poster shows reduced neuronal activity and altered network firing patterns in LRRK2 lines, indicating early functional changes before major cell loss.

Alongside this, Shikha presents evidence of deficits in autophagy lysosomal pathway function, including changes in DQ BSA signal and lysosome related proteins. These alterations appear to evolve over time, with LRRK2 neurons showing increasing divergence from wild type controls as networks mature. Imaging of synaptic markers further suggests that impaired lysosomal clearance may contribute to synaptic stress.

This work helps connect electrical dysfunction with disrupted autophagy in Parkinson models and provides a platform for investigating treatments that target cellular clearance pathways.

Thank you for following the full series of UKDRI Connectome poster features. This was just a small selection of all the incredible work on display.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Kristjan Holt at UKDRI Edinburgh. His work investigates how the antibody lecanemab interacts with amyloid beta at the level of individual synapses in the human Alzheimer disease cortex.

The poster explains that lecanemab has been shown to reduce amyloid plaques, yet less is known about how the antibody engages with the smaller pools of amyloid that sit on or near synapses. Kristjan uses high resolution imaging and three dimensional reconstruction to quantify more than one million synapses and identify antibody signal in both pre and postsynaptic sites.

The data shows clear colocalisation between lecanemab signal and synaptic structures, particularly within the halo that surrounds dense core plaques. This association is stronger in regions where synaptic loss is greatest, suggesting a possible link between antibody binding and vulnerable synapse populations. The work also raises questions about how clearance of amyloid beta by lecanemab may influence microglial responses and synaptic stability.

This study provides detailed evidence of where lecanemab acts at the microscopic level and helps refine our understanding of how antibody based treatments may affect synaptic health.

More posters from the series will follow soon.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Nathasia Mudiwa Muwanigwa at UKDRI UCL. Her work explores how tau pathology disrupts RNA at the synapse, a site that is central to communication between neurons and one of the earliest points of failure in dementia.

The poster uses the PS19 mouse model of tauopathy to track changes across three stages, from early synaptic dysfunction through neurofibrillary tangle formation to neuronal loss. Nathasia outlines how tau accumulation affects synaptic proteins, RNA transport and activity dependent RNA regulation. She then validates a method for isolating synaptosomes to perform targeted RNA sequencing, allowing detailed study of changes that occur directly at the synapse.

Initial findings show clear alterations in synaptic RNA profiles, with strong signals linked to complement activation and defects in transport pathways. These patterns point to disrupted molecular communication at the synapse and suggest that early tau driven changes in RNA may contribute to the progression of disease.

More posters from the series are coming soon.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Thomas Adams at UKDRI Imperial. His project focuses on developing a rapid point of care device that can detect urinary tract infections in people living with dementia, a group that often experiences delays in diagnosis due to communication difficulties and atypical presentations.

The poster outlines the need for a simple diagnostic tool that can identify infection early and reduce unnecessary antibiotic use. Thomas describes a human centred design process that involved carers and people living with dementia to ensure the device is practical, acceptable and easy to use. The system uses a molecular amplification method to detect bacterial DNA and provides a clear output suitable for community and home settings.

Validation tests in the laboratory show that the device can reliably identify infection signatures in a short time window, with clear separation between positive and negative samples. This demonstrates real potential for use in routine care, particularly in preventing sepsis and reducing hospital admissions.

More posters from the series will follow soon.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster Mei Kirby at UKDRI Imperial. Her work investigates how circadian rhythms are disrupted in people living with Parkinson disease and explores whether deep brain stimulation can help stabilise daily cycles of sleep, activity and vigilance.

The poster describes a combined approach that includes at home sensor monitoring, detailed sleep lab assessments and a stimulation protocol designed to modulate circadian timing. Mei outlines the main contributors to circadian disruption in Parkinson disease, including changes in sleep structure, reduced activity patterns and altered light exposure. The study integrates measures such as core body temperature, heart rate, mobility, home light readings, EEG and blood based markers to build a complete picture of rhythm stability.

Early data from the trial suggests that deep brain stimulation may influence circadian alignment in some participants, with changes seen in rest activity rhythms and selected physiological measures. The design also demonstrates how continuous at home monitoring can offer a realistic view of daily life patterns and symptom impact.

This work highlights the importance of circadian health in Parkinson disease and opens the door to new treatment strategies that support rhythm based wellbeing.

More posters from the series will follow.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Dr Ganna Leonenko at UKDRI Cardiff. Her work examines how plasma biomarkers and genetic risk scores relate to the diagnosis and clinical presentation of Alzheimer disease, aiming to understand why neuropathology and symptoms do not always align.

The poster presents data from a cohort of more than one hundred and ninety individuals, including Alzheimer cases and controls. Ganna reports that plasma measures such as A beta ratios and P tau levels show clear differences between groups, with P tau showing particularly strong predictive value. She also evaluates the roles of APOE genotype and a polygenic risk score, demonstrating that genetic factors make distinct contributions to diagnosis beyond biomarker profiles alone.

The study design highlights the importance of combining biological and genetic information when predicting disease state. Associations between biomarkers and risk scores help to explain the variation in clinical symptoms and strengthen the case for integrated diagnostic approaches.

More entries in our series will follow soon.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Gloria Cimaglia at UKDRI Cardiff. Her work explores whether retinal ganglion cells can act as an early signal of dysfunction in LRRK2 Parkinsonian models, providing a window into disease processes before motor symptoms appear.

The poster shows that retinal ganglion cells display measurable changes in mice carrying the LRRK2 G2019S variant. Gloria presents metabolic profiles from optic nerves that reveal clear differences linked to age and sex, as well as shifts in pathways that involve amino acids, lipids and energy related processes. Imaging data also highlights structural and functional alterations in retinal ganglion cells, suggesting that these neurons may respond to LRRK2 related stress earlier than brain dopaminergic cells.

Longitudinal analysis indicates that metabolic patterns evolve over time, with LRRK2 mice showing enrichments in pathways associated with mitochondrial stress and inflammation. This supports the idea that retinal tissue can provide a sensitive readout of early changes linked to Parkinson disease progression.

This line of work offers a promising foundation for developing non invasive markers that could detect early risk or treatment response.

More recordings from the series will follow.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Ziwei Chen at UKDRI Imperial. This project develops an unobtrusive radar based system for real time monitoring in dementia care, aiming to support safe and independent living for people with dementia.

The poster explains how radar on chip sensing can track movement, presence, room transitions and daily living patterns without cameras or wearables. Ziwei outlines an adaptive classifier that identifies activities such as walking, stationary states, absence from a room and vital movement signals. The system is designed for long term deployment, high privacy and low interference with daily life.

A living lab validation study involving twelve adults shows encouraging results. The classifier achieved strong performance in state detection and movement recognition, with clear potential for continuous room scale monitoring. The work also highlights the range of real world tasks used in testing, including reading, walking, making drinks and free movement through a home like layout.

This system offers a step toward practical monitoring that can support safety, understand behaviour changes and inform personalised dementia care.

More posters from the series will follow soon.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Dr Sam Neaves at UKDRI Cardiff. His work uses subgroup discovery to uncover patterns of regulatory crosstalk in dopaminergic neurons from Parkinson disease models, aiming to explain why these neurons fail in different ways across individuals.

The poster addresses a clear challenge. Dopaminergic neurons often appear to form a mixed bag of responses in Parkinson research, making it difficult to understand common pathways. Sam applies a GPU supported discovery framework to identify consistent regulatory groups within these cells, revealing three distinct failure modes linked to different cellular pressures.

The work also maps molecular networks that underlie these patterns, including regulatory circuits that define functional states within neurons. These states appear to influence vulnerability more strongly than classical identity markers. The poster shows how some states are driven by protein handling stress, others by metabolic limits, and others by disrupted signalling.

This approach offers a route to understand why dopaminergic neurons do not all fail for the same reason and how tailored interventions might be developed for different disease states.

More recordings from the series will follow soon.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Claire Pimblett at UKDRI University College London. Her work explores how the DNA repair factor FAN1 influences the expansion of CAG repeats in HTT, a process that drives progression in Huntington disease. Using iPSC derived neurons, the study investigates how FAN1 protects against repeat growth and how specific mutations alter this function.

The poster shows that FAN1 variants with reduced binding to MLH1 lose protective activity, allowing repeats to expand more readily. Claire also presents data showing that one FAN1 mutation increases the rate of repeat growth to levels similar to complete loss of FAN1. Fluorescent imaging and molecular assays illustrate how these changes affect both neuronal state and the behaviour of CAG tracts over time.

This work helps clarify the role of FAN1 in controlling repeat length and strengthens the link between DNA repair processes and disease progression in Huntington disease. It also raises questions about which FAN1 functions are essential for slowing repeat expansion in human neurons.

More recordings from the series are on the way.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Craig Terris at UKDRI Imperial College London. His work focuses on microglial autophagy in PD and PDD, a process that supports the recycling of proteins and damaged components inside cells and is vital for maintaining stability in the brain.

The poster explains that impaired autophagy is linked to PD and PDD, and that microglia may respond differently across these conditions. Craig presents data showing increased p62 in PD and PDD microglia, which suggests reduced autophagy activity. He also reports that microglial puncta counts near alpha syn inclusions differ between groups, with PDD showing fewer inclusions associated with microglia. This supports the idea that microglial engagement with protein aggregates may be altered in more advanced disease.

The work aims to clarify how microglial processes vary between PD and PDD and how these differences might contribute to disease progression. Craig outlines planned steps that include further analysis of autophagy markers and deeper investigation of links between microglial responses and alpha syn pathology.

More posters from the conference will be shared soon.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Dr Gaia Brezzo at the University of Edinburgh. Her work examines how the origin of myeloid cells shapes their behaviour and survival after ischaemic stroke, a condition that remains without effective treatments and often leads to lasting cognitive problems.

The study shows that stroke triggers widespread activation of resident microglia together with the arrival of infiltrating monocytes. These cells adopt distinct transcriptional states depending on both their origin and their position in the brain. Microglia enter reactive states that can persist long after the initial injury, while infiltrating monocyte derived macrophages remain largely restricted to the infarct zone and do not survive in the tissue over the long term.

The poster also highlights differences between connected brain regions, showing that distant sites can display altered microglial states even when they are not directly damaged. This suggests that cell origin and network connectivity shape the broader brain response to injury and may influence long term cognitive outcomes.

More recordings from the series will follow.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Lorenzo Capitani at UKDRI Cardiff. His work uses whole exome sequencing to study HLA variation and explores how antigen presentation may contribute to Alzheimer disease.

The poster shows how an algorithm for HLA typing from sequencing data was applied to more than two thousand individuals. This allowed the group to compare specific HLA alleles with Alzheimer disease status and identify which variants appear to offer increased or reduced risk. The work also links these findings to predicted changes in antigen binding sequences and possible effects on immune signalling in the brain.

Lorenzo highlights that stronger HLA resolution can reveal patterns that routine imputation may miss, opening the way for new questions about microglial responses and immune related mechanisms in dementia.

More recordings from the series will follow.

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Our @ukdementiaresearchinstitute Connectome series continues with a poster from Austeja Ciulkinyte at UKDRI Edinburgh. Her work explores how protein expression changes in brain parenchyma and brain vasculature during ageing, comparing findings in mouse and human tissue.

The study looks at bulk tissue and isolated vessels to understand how ageing shifts the abundance of specific proteins. The poster shows that large numbers of proteins change with age in both species, but the scale and direction of these changes can differ between parenchyma and vasculature. Austeja also highlights shared biological processes that are affected, including amino acid metabolism, synaptic function, extracellular matrix organisation and several pathways related to energy use.

The comparison of mouse and human datasets helps identify which ageing changes are conserved and which appear species specific. This supports better experimental design for ageing research and improves the use of mouse models when exploring mechanisms linked to dementia.

More posters from the conference will be shared as the series continues.

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Our series from the @ukdementiaresearchinstitute Connectome conference continues with another poster feature from the event. These short recordings highlight the work of researchers who are advancing our understanding of complex conditions.

This recording focuses on the poster ‘Development of variant specific antibodies to investigate the roles of CA B variants in schizophrenia risk’. The work is presented by Kirsten Baillie from UKRI Cardiff, who explains how antibody development can support the study of CA B variant expression and the possible links to schizophrenia risk.

More posters from the conference will be shared as the series grows.

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Our series #posterinashort from the @ukdementiaresearchinstitute Connectome conference continues with another recording from the poster hall.

This recording focuses on the poster titled Novel Anti Clusterin Monoclonals as Tools for Characterising Clusterin Expression in Biofluids and Tissues. The work is presented by Robert Byrne, who outlines how newly developed monoclonal antibodies can support the study of clusterin expression across tissues and biofluids in neurodegenerative research.

More recordings from the conference will follow as the series builds.

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Our series from the @ukdementiaresearchinstitute Connectome conference in Manchester continues, sharing short recordings that highlight posters and the people behind the research.

This feature focuses on the poster ASTROCYTE RESPONSES TO DIFFERENT PATHOLOGIES IN PARKINSON'S DISEASE. The work is led by Dr Anna Mallach and presented by Sasvi Wijesinghe, who outlines how astrocytes respond to varied disease related challenges in Parkinsons Disease and why this matters for understanding disease processes.

More recordings from the event will follow soon.

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This week we’re at the​ @ukdementiaresearchinstitute Connectome conference in Manchester - with more #researchinashort talks. Here we have Dr Mizuki Morisaki sharing her poster on high endocytic polygenic risk in late onset Alzheimer Disease using iPSC microglia. A quick look at how genetic risk shapes microglial behaviour. #dementiaresearch #gentics

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