Alzheimer’s disease (AD) is the most common form of age-related dementia. Currently affecting 50 million people worldwide, this number is set to rise to 152 million by 2050. With an ever-increasing necessity for better treatments and therapies, research is vital to validate new drug targets, identify potential mechanisms and improve the success of clinical trials.
The Alzheimer’s Research UK (ARUK) Conference 2018 commenced in the heart of London at the iconic Queen Elizabeth II Centre. The conference encompassed the progressive research undertaken by institutions across the UK, with a mission to prevent, treat and hopefully find a cure for dementia.
Opening remarks and a personal perspective
The conference opened with Diane Hanger (King’s College London (KCL), UK) welcoming the 650 delegates and introducing the first speaker: Hilary Evans, Chief Executive of ARUK. Hilary took to the stage where she announced the milestone achievements of ARUK over the past year, including a record breaking 44% increase in public donations. She also launched the new #ShareTheOrange campaign video starring Bryan Cranston, which they hope will challenge perceptions and educate people about the reality of dementia (you can watch the campaign here).
Hilary then introduced Rick Somerset-Williams, who shared his incredible personal perspective of dementia in memory of this mother. He took us through an immersive and powerful life journey into the hardships and emotional struggle that Alzheimer’s can take on both the person and their family. Rick’s pursuit in fighting for this cause provided the hope that fuels the work being conducted by ARUK and researchers striving to defeat dementia.
Flash talks hosted by Elizabeth Glennon (KCL) changed the pace with ten PhD and early career researchers lighting the stage with their innovative research. Topics included non-invasive MRI techniques for brain clearance pathways, microglia formation in response to toxic pathology, endoplasmic reticulum–mitochondrial interactions in Alzheimer’s, and many more. These face-paced talks from early career researchers certainly gave attendees food for thought, and generated some great discussion throughout the rest of the conference.
The UK Dementia Research Institute (UK DRI)
After the morning coffee break, the focus turned towards the UK DRI, a new network of research centres across institutions in the UK, launched in 2017. First, the Institute’s Chief Operating Officer, Adrian Ivinson, discussed the UK DRI’s achievements and priorities since launch. On the backbone of David Cameron’s £250 million initiative for dementia, Adrian highlighted the immense knowledge gap in the field and emphasized the importance of the UK DRI attracting the best of people, developing a culture of excellence and collaboration, greater public awareness and new ideas for treatment and prevention.
Adrian then showcased the scientific research at the UK DRI Hub at University College London (UK). These include studying gene expression and biological pathways in single cells; biomarkers; early axonal transport deficits; and mechanisms of synaptic failure.
Next, we heard from research leaders from the five further centers across the UK. First, Giovanna Malluci (UK DRI Associate Director for University of Cambridge, UK) introduced the Cambridge center, which will focus on delivery of transformative interdisciplinary basic science that drives translation by looking at early disease processes at the cellular, biophysical and chemical level.
Cardiff University (UK) UK DRI Associate Director Julie Williams continued, presenting her group’s approaches that will use genetics and immunology expertise in bioanalytics, functional genomics and specialist imaging in dementia research.
Tara Spires-Jones (Edinburgh University, UK) presented Edinburgh’s focus: with a non-neuronal centric view, they aim to understand the contributors to circuit dysfunction and interactions between various cell types.
Paul Matthews (UK DRI at Imperial college London, UK) interestingly drew attention to the impact of the environment and lifestyle on dementia. His team will investigate the biological underpinnings of these multiple factors with drug discovery, sleeps studies and regulation of synaptic health.
The final UK DRI Associate Director, Chris Shaw from KCL, described the KCL center’s approach to frontotemporal dementia, investigating proteostasis, RNA binding and synaptic physiology and toxicity, all of which will allow a different perspective on dementia research.
The session was followed by a panel discussion with UK DRI Associate Directors and Adrian Ivinson. Questioned on the practicalities of creating a unified Institute with centers spread across the UK, as well as aspects of training opportunities, the panel disclosed that the joint supervision of PhDs and post-docs, shared resources and conferences are all in the planning stages, and reiterated the focus of the DRI on collaboration and innovation.
Synaptic function in Alzheimer’s disease
Lunch and poster sessions followed giving the opportunity for delegates to network and engage with exciting research. The afternoon session then kicked off investigating synaptic dysfunction, thought to be the leading cause for cognitive impairment in AD, chaired by Peter Giese (KCL).
“It is not about yes or no in terms of pathology but more about how and when.”
Johannes Attems (Newcastle University, UK) started the session highlighting the requirement for better quantitative measures for the identification of neuropathological hallmark lesions for several overlapping diseases. He described the use of tissue arrays to characterize age-associated neurodegeneration such as distinct clinical phenotypes, synaptic loss and white matter integrity: “It is not about yes or no in terms of pathology but more about how and when.”
The session continued with Tara Spires-Jones (University of Edinburgh, UK) who described her group’s novel findings concerning the role of ApoE4 and clusterin in exacerbating synapse loss, and the consequential effects of this on amyloid-β accumulation. Dr Spires-Jones’ new technological advances with the use of array tomography will hopefully provide a new avenue for investigating synaptic composition and potential targets for therapeutic intervention.
Kei Cho (KCL) followed in succession posing the question: is ‘synaptic weakening’ a critical step in the early pathophysiology of Alzheimer’s? His newly identified ‘Protein X’ involved in tau mis-localization is definitely on the watchlist as a potential molecular target.
Concluding the session, fascinating data was presented by Beatriz Gomez Perez-Nievas (KCL) demonstrating a role for astrocytes in synaptic health in AD. With the use of primary astrocytic and neuronal cultures, she was able to induce a tau-dependent synaptic loss in response to amyloid-β.
After a final coffee break, ARUK Chief Scientific Officer David Reynolds updated the delegates with ARUK’s research successes. ARUK has supported £14.4 million of new research projects over the last year, with further investments planned for the development of the Dementia Consortium, Brains for Dementia Research, Dementia Statistics Hub and Join Dementia Research platforms, which all aim to enhance the quality of ongoing academic research.
Presenilins in AD
The final session of the day discussed the roles of presenilins in AD; a group of genetic mutations, which can lead to more familial forms of the disease. From Harvard University (MA, USA), Jie Shen provided insights on the essential role of presenilins in synaptic plasticity in the aging brain.
Continuing this theme, Radek Dobrowolski (Rutgers University, NJ, USA) illustrated that a deficiency in presenilins can dysregulate lysosomal nutrients indicated through remarkable calcium imaging. Paola Pizzo (University of Padua, Italy) presented the final talk of the day, looking specifically at Presenilin 2 deficiencies, which may impact endoplasmic reticulum– mitochondrial functionality, cellular bioenergetics and autophagy, a mechanism for cellular clearance.
The ARUK conference 2018 was a fantastic event, hosting world leading experts along with inspired early career researchers, PhD students, industry partners and sponsors unified in one goal: the fight to conquer dementia. Speaking to some of this year’s attendees, Grace Hallinan (University of Southampton, UK) said: “this year’s ARUK conference was a great event, that gave us the opportunity to network with some of the UK’s best dementia researchers.” John Hardy (UCL, Brain Prize Winner 2018) thought “there was a great variety of topics especially in leaps of genetics and new technologies.” Overall, the fight against dementia was epitomized in the ARUK Conference, with new ideas, collaborations, and a drive to succeed being at the forefront of all the sessions and discussion. We look forward to hearing more about these at the next conference in Harrogate (UK) in 2019. A huge thanks to ARUK for this year’s event and their continued investment in dementia research, and we hope that with this research we can make a difference to the lives of those living with dementia.
Biography – Huzefa Rupawala
Huzefa began his journey into the neuroscientific field after graduating with a Neuroscience BSc from KCL. Diverting into new avenues of research he completed his MRes in Biomedical and Translational Science and finally commenced his PhD in Neuroscience in the labs of Peter Giese and Wendy Noble at King’s. His research interests lie in understanding the regulation of synapse health in AD, specifically the role of cysteine string protein alpha, a multifunctional synaptic protein.