More Diversity Needed in Dementia Studies to Enhance Targeted Therapies

A lack of diversity in genomic studies for dementia could limit the effectiveness of targeted therapies across underrepresented populations, finds research by UCL experts.

Results from two papers that explore regions of the genome associated with Alzheimer's disease and dementia in African populations will be presented at the Future of Dementia in Africa conference.

The results highlight discrepancies in the genetic causes of Alzheimer's in African populations compared to Caucasian populations.

Work led by Professor Henry Houlden (UCL Queen Square Institute of Neurology) alongside colleagues in Nigeria, India and other South and Central Asia countries, explored around 1,000 clinical samples from patients in Africa and other diverse populations, who had a fatal type of motor neuron disease called Amyotrophic lateral sclerosis (ALS).

ALS can cause cognitive changes and potentially lead to symptoms of dementia.

The team focused on the common genetic causes of ALS and related disorders—including an increase in the C9orf72 gene (which is abundant in nerve cells in the outer layers of the brain). C9orf72 is one of several genes that are currently the focus of trials for new treatments for ALS.

The researchers also screened for other causes of ALS and are now planning a genome wide association study (GWAS).

Using new long-read sequencing techniques (to read long strands of DNA in one go) the team were able to generate preliminary data and analyze different populations to define the extent of C9orf72 spread, mosaicism (the presence of more than one genotype in an individual) and the presence of gene mutations.

Many patients have currently never had gene screening, so this breakthrough could have important implications for ALS and ALS-dementia patients worldwide.

Meanwhile, researchers led by Professor John Hardy (UCL Queen Square Institute of Neurology) and Professor Njideka Okubadejo (University of Lagos), alongside partners across Nigeria, will also present preliminary results from a second ongoing GWAS of Alzheimer's disease in a Nigerian population.

The analysis found a negligible effect from the gene APOE4—a major genetic risk factor for Alzheimer's disease in people of European descent—in a cohort of nearly 1,200 individuals.

The study also identifies unique, disease-relevant regions of interest in the Nigerian population (such as different tribal groups), and emphasizes how diversification of GWAS studies is crucial for uncovering more universal knowledge about neurodegenerative diseases that will better serve all populations.

Professor Houlden, who was involved in both studies, said, "We are excited to share our data with researchers at the Future of Dementia in Africa conference, because people in African populations are underrepresented in research into dementia and other neurodegenerative conditions.

"We are keen to expand our network and carry out further genome-wide association studies in different populations, to identify new risk factors and advance treatments through work with clinical teams."

Professor Njideka Okubadejo from the University of Lagos said, "Disease genetics are not uniform across populations and it is crucial that genetic research extends beyond European populations so we can develop more effective treatments. In order to achieve this goal, genetic research must also be more inclusive and accessible to more researchers."

Dementia is a growing public health challenge around the world, with an estimated 150 million people expected to be living with the disease by 2050. Africa is no exception, with an estimated 2.13 million people living with dementia in sub-Saharan Africa in 2015. This number is expected to increase to 3.48 million by 2030 and 7.62 million by 2050.

Africa faces unique challenges in addressing dementia, including limited resources, varying levels of health care infrastructure, and a need for greater awareness and education. This conference represents a pivotal moment for the continent, offering a chance to consolidate efforts, share knowledge, and develop strategies tailored to Africa's specific needs.

Dr. Mie Rizig (UCL Queen Square Institute of Neurology), who is on the scientific committee for the Future of Dementia in Africa conference, said, "Global partnerships are crucial for enhancing neurodegenerative research productivity in low- and middle-income countries, particularly in Africa. We are thrilled to see these promising data from teams at UCL and Nigeria and eagerly anticipate more successful collaborations arising from this conference."