Alzheimer’s Risk Factors Examined in First North African Study
The North African Dementia Registry (NADR) will collect multiomics data from North African populations.
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Disease etiology and manifestation vary across different populations, which can have implications for diagnosis and treatment success. A growing number of research projects are prioritizing diversity in study recruitment and collecting biological data from a wider range of individuals. This can help scientists and clinicians understand population differences and tailor diagnostic and treatment procedures accordingly.
The North African Dementia Registry (NADR) is a new, large-scale project – the first of its kind – which will collect multiomics data from North African populations. The NADR aims to improve our understanding of how genetic and environmental factors contribute to the risk of Alzheimer’s disease (AD) and other dementias in diverse global populations.
Spearheaded by The Davos Alzheimer’s Collaborative (DAC), the project also has support from The Institute of Global Health and Human Ecology (I-GHHE) at The American University in Cairo (AUC), The UCL Queen Square Institute of Neurology, University College London (UCL) and a partnership with long-read sequencing technology provider, PacBio.
Technology Networks recently had the pleasure of speaking with Dr. Vaibhav Narayan, executive vice president and head of strategy and innovation at the DAC, Dr. Mohamed Salama, MD, professor and NADR lead at I-GHHE and Dr. Mie Rizig, UCL NADR lead and clinical senior research fellow at UCL. We discussed the origins of the NADR project, why the collection of multiomics data versus single-omics data is critical and the future of AD research.
What do we know about how our genetics can influence AD risk?
Vaibhav A. Narayan, PhD, MBA (VAN):
This is a complex question. There is a rare but familial version of AD in which just a few genes determine almost the entire risk for the disease. The more common version of Alzheimer’s has a significant genetic component – by some estimates, ~70% of the overall risk can be explained genetically – but the genetic risk is spread across 100s, maybe even 1000s of genes, each of which contributes only a small fraction towards the total genetic risk.
At this time, the known genetic mutations can only explain about 10% of total variation in risk. The APOE gene is the most significant risk gene known. However, it is important to note that composition of genetic risk varies across races and gender. Therefore, it is important to study the genetics of Alzheimer’s across diverse geographies and populations.
MC:
Why is looking at Alzheimer’s through a multiomics lens important for understanding the disease further and developing effective diagnostics/treatments?
VAN:
Multiomics here refers to collecting data using different modalities that measure different types of molecules within the body (genomics – DNA, transcriptomics – RNA, proteomics – proteins and metabolomics – metabolites).
Understanding and unraveling the mechanisms that drive a complex disease such as AD requires studying underlying biology at multiple molecular levels using a multiomics approach. Different modalities of a multiomics approach can contribute to diagnostic and treatment development in different ways. For example:
- Genomics data can lead to better genetic tests of AD risk.
- Transcriptomics could lead to new targets for gene therapy.
- Proteomics studies can lead to better blood-based biomarkers as well as new targets for small- molecule or antibody drugs.
- Metabolomics can lead to insights on how toxins, diet and pollutants impact AD progression.
Credit: iStock.
MC:
When was the NADR set up, and why is there a need for a diverse multiomics dataset in the context of AD?
Mohamed Salama, MBBCH, DTQM, PhD (MSMD):
The vision for NADR started three years ago after the Egyptian Dementia Registry Network (EDN), a research dementia registry covering Egypt, was created. Thanks to DAC funding, this was expanded to plan a registry network that covers North African countries adopting the same procedures applied in the EDN.
The network is composed of a central hub in each country that coordinates standard operating procedures for data and sample collection. The idea of using a multiomics approach emerged from the fact that dementia is a complex neurodegenerative disease with an underrepresentation of different populations. To have a complete picture of the disease, we need multidisciplinary teams that work in different geographic locations – NADR is filling this gap in North Africa.
MC:
Why hasn’t this been done before?
VAN:
Efforts such as our NADR multiomics project require local human resource capacity, organizational commitment, technical capability, multi-disciplinary collaborations (often international), a unified driving vision and funds.
The collaboration between American University Cairo, University College London, Davos Alzheimer’s Collaborative and PacBio, has helped us to bring these key ingredients together to enable such work.
MC:
Can you discuss the core technologies that will be adopted to build this dataset, and why advanced next-generation sequencing tools such as long-read sequencing will be important?
Mie Rizig, MD (MR):
The cohort aims to generate scientific insights that can be efficiently translated into clinical applications, including diagnosis, risk stratification and inclusion in therapeutic trials. Identifying genetic risk factors alone is not sufficient; the key lies in translating these findings into meaningful clinical and therapeutic outcomes.
To this end, we will employ cross-cutting technologies such as long-read sequencing of both DNA and RNA, which offer superior capabilities in uncovering disease-causing mechanisms. These include repeat expansions, structural variants, transposable elements, splicing variants and transcript isoforms, along with complex regulatory processes such as post-transcriptional regulation, mRNA stability and methylation.
When integrated with conventional clinical data, innovative digital health records and biomarkers derived from this cohort, these advanced technologies have the potential to drive transformative discoveries.
The resulting insights will not only benefit populations in North Africa but will also contribute to the global advancement of precision medicine and therapeutic innovation.
MC:
What are your hopes for the short- and long-term future of Alzheimer’s research?
VAN:
In the short term, our hope is that data from under-represented regions like Africa is available to researchers around the world, such that it is used to better understand disease causal mechanisms and the underlying biological heterogeneity of this complex disease.
In the longer term, we hope that the data and insights generated from efforts such as the NADR multiomics study lead to more customized diagnostics and therapeutic solutions that improve outcomes in diverse patient populations across the world.
