Print This PostMy research throughout my PhD, and now in my first postdoc, is focused on Alzheimer’s disease in people who have Down syndrome. In early June, I attended the International Trisomy 21 Research Society (T21RS) conference in Rome. T21RS is the only official society for Down syndrome research, and the bi-annual conference hosts researchers who study all aspects of Down syndrome, from the heart to the immune system, to lifestyle interventions. This conference marked the 10-year anniversary of the society. I was lucky enough to attend the previous T21RS conference in Long Beach California in 2022, so this felt like a really nice check in to hear about all the advances in the field over the past 2 years.
So why is a Down syndrome conference so focussed on Alzheimer’s disease? Alzheimer’s disease research is a huge focus of this meeting, as people with Down syndrome are at a very high risk to develop Alzheimer’s disease. Down syndrome is caused by trisomy of chromosome 21, the smallest human chromosome, which encodes just over 200 protein coding genes. Among the genes on chromosome 21 is the amyloid precursor protein gene, or APP. APP is cleaved in the brain to produce the hallmark pathology of Alzheimer’s disease, the amyloid-β plaques. As people with Down syndrome have three-copies of APP, this protein is cleaved to produce more amyloid-β which is the known cause of Alzheimer’s disease in Down syndrome. People with Down syndrome also develop both the pathology and clinical symptoms of dementia decades earlier than in the general population.
The conference was hosted in Rome, with the first day being a “satellite symposium” hosted at Sapienza University. On this day, the conference was broken into a preclinical and a clinical stream. I attended the preclinical talks where many models for Down syndrome research were discussed. A large focus of the Q&A was induced pluripotent stem cells (iPSC). In the Down syndrome field, it is widely accepted that the best practice is to use a trisomic iPSC line that has a paired isogenic euploid control. To date, these have largely been generated from rare individuals who are mosaic for trisomy 21, meaning that not every cell in their body has three-copies of chromosome 21. These isogenic pairs are technically difficult to produce, and so publicly available trisomic/euploid iPSC pairs are very few in number. Although no clear consensus was reached, it was highlighted that for reproducible research, more pairs generated from independent individuals are required to be used in experiments going forward. But importantly, ECR members of the panel also stressed the practical difficulties this may place on the people actually carrying out the lab work. I thought that this was an interesting way to open the conference, with many people reflecting on this session in their own talks throughout the remainder of the meeting.
The remaining three conference days were hosted in La Nuvola conference centre, with over 500 attendees and more than 200 research posters on display. As someone who spends every conference I attend looking for the Down syndrome related posters, I was overwhelmed by the need to visit each and every one.
One major theme of this conference was how anti-amyloid-β monoclonal antibody therapies could be made accessible for people who have Down syndrome.
In the opening keynote, Professor Sir John Hardy spoke about how the amyloid cascade hypothesis of Alzheimer’s disease really has foundations from Down syndrome research. He urged that now is the time for clinical trials to be conducted for these therapies in people who have Down syndrome, emphasising that people with Down syndrome are identified from birth, and so the issue of early identification of who to treat will not be as difficult as it can be in the general population. It was also exciting to see an industry session hosted at the conference, where pharmaceutical companies including Lilly and Alzheon were on the panel. Despite good intentions, it was disappointing to hear that none of the companies represented on the panel are currently planning or conducting their own trial for this population, showing that there is still a long way to go, and advocacy from researchers and the Down syndrome community for independent clinical trials will be very important.
This conference was also the first time that I proposed and chaired a symposium and marked my first talk at an international conference. This was an intimidating but an overall enjoyable experience, where I received a lot of insightful feedback. My session focussed on omics approaches to Alzheimer’s disease in Down syndrome, and many large datasets were presented from post-mortem brain tissue and biofluids which will be important resources for the research community moving forward.
A second major theme very relevant for Alzheimer’s disease research was the focus on Down syndrome as an interferonopathy. People with Down syndrome have three-copies of a cluster of four interferon receptor genes, including IFNAR1 and IFNAR2. A second keynote talk by Dr Kelly Sullivan really focussed in on this, where the work of his group has shown heightened interferon signalling in the peripheral immune response of people who have Down syndrome. Now they, along with other labs, are also exploring how this may affect the development and progression of Alzheimer’s disease in Down syndrome, using preclinical models, and clinical samples. People with Down syndrome have an overall perturbed immune response, which is now believed to extend to how the brain responds to pathological insult.
By far the best aspect of this conference was the effort made to include people with Down syndrome and their families within the event. Two of the conference days hosted a parallel session for people who have Down syndrome, their families, and carers. Talks about research, as well as practical sessions for skill development were hosted. The final session of the conference brought together all attendees; researchers, families and people who have Down syndrome.
We heard brilliant inspirational speeches and panel discussions from advocates who have Down syndrome, including Italian national athletes in gymnastics and synchronised swimming.
Not only did the conference make accessibility a priority for attendees with Down syndrome, but researchers attending the conference had access to free childcare in the conference venue. Parents using this service who I spoke to thought that it made their attendance at the conference easier – this seems like a great initiative that would be a welcome sight at other conferences. Other really nice touches that made attendees feel very welcome in Rome included providing free metro tickets and free entrance to Rome’s Capitoline museum. At the opening ceremony we were also joined by the mayor of Rome who welcomed us to the city, and moreover, the conference even received a letter from the pope to commend it taking place in Rome!
Clíona Farrell
Author
Dr Clíona Farrell is a Postdoctoral Researcher in the UK Dementia Research Institute at University College London. Her work focuses on understanding neuroinflammation in Down syndrome, both prior to, and in response to, Alzheimer’s disease pathology. Originally from Dublin, Ireland, Clíona completed her undergraduate degree in Neuroscience in Trinity College, and then worked as a research assistant in the Royal College of Surgeons studying ALS and Parkinson’s disease. She also knows the secret behind scopping the perfect 99 ice-cream cone.
Dementia Researcher
