Highlights from ARUK 2022

The Alzheimer’s Research UK Conference was held in Brighton, UK, on 1-2 March 2022. Leading experts discussed the key topics in Alzheimer’s research and a range of recent study data was presented. In this feature, we cover the biggest topics from the conference, so you can stay up-to-date on the latest in Alzheimer’s research.

Psychosis in Alzheimer's Disease

A big topic of discussion at ARUK 2022 was the connection between psychiatric diseases and Alzheimer’s disease (AD). Roughly 40-50% of patients with AD experience psychotic symptoms, such as hallucinations and delusions.^1,2 Psychosis can be very distressing to both patients and caregivers and has a great impact on quality of life. There is not yet a specific treatment for psychotic symptoms in patients with AD.

We spoke to Byron Creese, PhD, of the University of Exeter, who explained recent research that suggested that the appearance of neuropsychiatric symptoms in people who do not have any cognitive issues could be an early sign of neurodegenerative disease.³

Dr Creese also discussed the genetics involved in psychosis in AD. A recent genome-wide association study of 12,000 patients with AD plus psychosis reported a link between variation in two gene loci (ENPP6 and SUMF1) and psychosis.² Links have also been found between the genetics of other psychiatric conditions, such as schizophrenia and bipolar disorder, and psychotic symptoms in AD.

Ioanna Katzourou, MBBS, MSc, a PhD student at Cardiff University, presented a study which used a polygenic risk score analysis to assess genetic links between AD plus psychosis and three common neuropsychiatric disorders – schizophrenia, bipolar disorder, and depression. The study found a significant positive association between the genetic variations found in patients with schizophrenia or depression and those with AD plus psychosis. This suggests that there could be similar mechanisms causing psychotic symptoms in each of these diseases. Further research is needed to investigate which specific mechanisms or pathways could be involved.

In terms of treatment options for AD plus psychosis, the selective 5-HT2A inverse agonist, pimavanserin, has been trialed in Phase II and III studies (NCT02035553, NCT03325556), with promising results. The drug has already been approved by the FDA for use in patients with Parkinson’s disease who are experiencing psychotic symptoms.³

Biomarkers and Diagnostics

Another hot topic in AD research is the development of new biomarkers and improved diagnostic criteria. Early identification of AD could provide opportunities to attempt to delay disease progression.

We spoke to Sarah Wilson, MSc, of Newcastle University, about the Early Detection of Neurodegenerative diseases (EDoN) initiative. The project aims to use digital technology to monitor changes in volunteers’ behavior and health before obvious symptoms of neurodegenerative disease develop, in an attempt to identify the onset of dementia-causing diseases at their earliest stages.

We also discussed imaging biomarkers with Pawel Markiewicz, PhD, of University College London, who talked about recent advances in PET-MRI scanners. The rise of PET-MRI has allowed broader research into imaging biomarkers, which has provided useful data about the progression of AD.

Gut Microbiome in Alzheimers Disease

The pathogenesis of AD is still not well understood, but recent research has suggested that the gut microbiome may play an important role. ARUK 2022 saw a lot of discussion about the gut microbiome and its possible effects in AD, including a presentation from Edina Silajdzic, PhD, of King’s College London, about the immunoregulatory role of the gut microbiome in AD.

Research has shown that the gut microbiota is different in up to 85% of patients with AD, compared to people without AD.⁴ Dr Silajdzic discussed how alterations in gut microbiota can cause changes in short-chain fatty acids, which in turn could affect microglia. Levels of inflammatory cytokines, which are released by microglia, have been shown to be increased in the blood of patients with AD. There are strong correlative links between the gut microbiota and AD, but more research needs to be done as to whether the links are causative.

We also spoke to Cornelia van Duijn, PhD, from the University of Oxford, about the microbiome and AD. A key area in AD pathogenesis research is investigating the effect of the gut-brain axis on disease onset and development. The gut microbiome determines levels of metabolites in the blood, which have a big effect on brain function.

Research has suggested that many patients have a change in the gut microbiome before developing AD, which could provide crucial clues about the causes of the disease. These changes could be due to a variety of reasons, from genetics to lifestyle. Prof. van Duijn emphasized the importance of studying the role of the gut-brain axis to better understand the pathogenesis of AD.

Synaptic Network Dysfunction

Changes in synapses and neuronal circuits are a key area in AD research. There were several presentations at ARUK 2022 on dysfunction in synapses and neuronal networks. Afia Ali, PhD, of University College London, explained how research into changes in neuronal circuits could help with delaying disease progression.

In AD, the excitatory-inhibitory balance among neurons is disrupted, and the brain enters a hyperexcitable state. This leads to dysfunctional proteins, such as amyloid-beta and tau, spreading faster through the brain. It is hoped that by investigating the causes of this hyperexcitability, researchers can find ways of stopping it, thereby delaying progression of disease. Delaying progression of disease is a crucial aim of AD research, as this allows patients to have a better quality of life for longer and creates opportunities for interventional treatment.