Tackling the growing burden of noncommunicable diseases in Africa through scientific collaboration: The case of Alzheimer’s disease

One of the significant achievements of our times is the consistent increase in the lifespan of humankind. Over the course of a century, we have progressed from scarcely any nations having life expectancies surpassing 50 years, to now over 40 countries where life expectancy exceeds 80 years. Today, it’s common for individuals to anticipate living well into their sixties and beyond.

According to the World Health Organization, the segment of the population aged 60 years and older is projected to reach 2.1 billion by 2050 (compared to 1 billion in 2020), while the number of individuals aged 80 years or older is anticipated to triple between 2020 and 2050. Two-thirds of the world’s population over 60 years old will reside in low- and middle-income countries and the number of older persons is expected to grow fastest in Africa, where the population aged 60 or over is projected to increase more than three times by 2050.

Older adults suffer from certain noncommunicable diseases that are commonly associated with aging. In the past, the burden of disease in Africa primarily stemmed from communicable, maternal, neonatal and nutritional diseases. However, given the aging trends and changes in lifestyle in several African countries, there has been a notable increase in the incidence of noncommunicable diseases and its related disabilities continent-wide. Projections indicate that noncommunicable diseases will soon surpass the former as a predominant health concern, and local health systems will confront significant challenges to meet the care needs of their aging population.

A particularly debilitating noncommunicable condition affecting the elderly is Alzheimer’s disease (AD). AD predominantly involves neuronal loss (named neurodegeneration) and cognitive decline leading to a progressive impairment of functions like memory and autonomy. Fostering pioneer scientific research and strengthening local capacity are key to tackle the rapidly growing burden of AD in the African context.

International collaboration and an innovative way to look at Alzheimer’s disease

A project supported by the Joint Canada-Israel Health Research Program is investigating the physiological changes in a specific type of brain cells called microglia and their links to AD’s development and progression. The project is co-led by Professor Marie-Eve Tremblay (University of Victoria, Canada), Dr. Benneth Ben-Azu (Delta State University, Nigeria) and Dr. Dan Frankel (Tel-Aviv University, Israel). 

Microglia, the immune cells of the central nervous system (CNS), have recently gained recognition for their pivotal role in maintaining brain health. These cells play a significant role in determining brain balance, facilitating the clearing of harmful substances, improving cognitive abilities and reducing brain damage associated with viral infection, aging and AD pathology. Neuroscientists have already discovered that senescence, an important cellular response to aging, is instrumental in disrupting brain function and structure. 

In spite of being armed with this knowledge about these CNS immune cells and the cellular response to aging, questions on how to use this knowledge to protect the brain from the effects of aging, such as AD, remain unanswered. Little is known about whether senescence of microglia cells results from aging, infections or brain diseases, or alternatively, if it causes these processes therefore contributing to the onset or progression of AD.

The increase of the aging population in Africa expected over the next decades is coupled with the scarcity of basic and translational science — or science that directly benefits people — related to dementia on the continent. The situation calls for investments in local scientific capacity and fostering international collaborations for AD research to uncover opportunities for treatment of AD patients in Africa and across the world.

The research team leading this project hypothesizes that the presence of cellular senescence-induced changes in microglial cells accelerate neurodegeneration and brain conditions, while their removal would relieve several age-related brain disorders. They take advantage of the complementary expertise of the three research sites to conduct state-of-the-art experiments and molecular analyses of senescent microglia.

Using brain samples from modified humanized mouse models of AD— that is, mouse strains containing functional human genes, cells or tissues, the investigators are evaluating the consequences of viral infections in AD pathology by causing a rise in senescent cells. This bi-directional approach is unique and has potential immediate applicability in testing the effect of senolytics, an emerging class of drugs that selectively kill senescent cells and have been shown to extend the lifespan in animal models. 

Strengthening African scientific talent in neuroscience research 

This project has catalyzed the establishment of the DELSU Joint Canada-Israel Neuroscience and Biopsychiatry Laboratory, a new research centre at the Department of Pharmacology, Faculty of Basic Medical Sciences, at Delta State University in Nigeria. The laboratory, led by Dr. Benneth Ben-Azu is unique as it is the first of its kind to be situated in the southern part of Nigeria with primary research activities focused on neuroscience experiments and neuropsychiatric conditions. 

The goal of Ben-Azu and his team is to enlarge their network of scientific collaborations to design novel therapeutic strategies that specifically target markers of brain alterations at the molecular and clinical levels in the context of the diversity of African genomes and their interactions with the local environment. The research will provide evidence that can be used to prevent and treat not only AD, but also other neurological diseases in which microglia are implicated, such as schizophrenia, autism, attention deficit hyperactive disease, epilepsy, anxiety, major depressive disorders and Parkinson's disease. 

The weight of these diseases impacts not only patients but also extends to their immediate family, caregivers and the broader health and socio-economic systems within the community. In Africa, as well as in numerous other underserved populations, health care faces additional challenges due to globalization, inequalities and the gradual decline of essential informal support networks, such as multi-generational family setups crucial in the provision of care. Consequently, the continent must establish strong scientific capabilities, leveraging global progress in research for prevention, treatment and rehabilitation for AD and other disorders.

By investing in the future of this research in Africa, the laboratory will reduce the current gaps in knowledge regarding AD and other neurological conditions on the continent and contribute to improving research capacity by supervising post-doctoral fellows from Nigeria and other African countries. At the moment, over 15 students, consisting of 4 PhD students, 9 master’s students, 1 post-doctoral fellow, and 1 lab manager/administrator with 2 research assistants from the region are being supported by the lab. 

Next steps

Understanding the mechanisms that lead to senescence of microglial cells may reveal new targets for treatment of AD and similar neurodegenerative diseases linked to aging and infection. Findings from this project could help to explain why medications used to treat AD do not work.  These results could also increase the rationale for testing senolytics as a treatment to stop, reduce or even reverse the symptoms of AD, while strengthening scientific capacity in Africa for a broader global impact. 

Contributor: Fabiano Santos, senior program specialist, IDRC