A new international study has identified key genetic factors that may protect against Alzheimer’s disease (AD), offering valuable insights into the biological mechanisms of this devastating condition.
The research, led by the Hong Kong University of Science and Technology (HKUST), focused on genetic variations in East Asian populations, including Chinese and Japanese individuals, as well as European populations.
Alzheimer’s disease affects more than 50 million people worldwide and is one of the leading causes of dementia. It gradually damages memory and cognitive function, ultimately interfering with daily life. Despite decades of research, effective treatments remain limited, largely due to the complexity of the disease and the difficulty in finding suitable drug targets.
One of the most promising genetic factors linked to Alzheimer’s risk is the SORL1 gene (Sortilin-Related Receptor 1). The SORL1 protein helps regulate the production and removal of amyloid-beta, a toxic protein that builds up in the brain and contributes to Alzheimer’s disease.
Previous studies in European populations suggested that certain variants of SORL1 might provide protection against the disease, but little was known about how these variants function in other ethnic groups.
To address this gap, a multidisciplinary team led by Professor Nancy Ip of HKUST conducted a large-scale genetic study across diverse populations. The study involved researchers from University College London, Niigata University, and the Shenzhen Institutes of Advanced Technology, among others.
They analyzed genetic data from individuals in mainland China, Hong Kong, Japan, and Europe, incorporating information from major international databases such as the Alzheimer’s Disease Neuroimaging Initiative.
The study uncovered a key genetic variant, called Hap_A, which was found to offer strong protection against Alzheimer’s disease in East Asian individuals. Interestingly, this variant is extremely rare in European populations, with East Asians being 168 times more likely to carry it.
Individuals with Hap_A showed better cognitive function, reduced brain degeneration, and milder Alzheimer’s pathology compared to those without the variant.
Further analysis revealed that different ethnic groups have unique sets of SORL1 variants that help protect against Alzheimer’s. This suggests that genetic influences on the disease vary by ancestry, highlighting the importance of studying diverse populations to fully understand Alzheimer’s risk and potential treatments.
To explore how these protective variants work, the researchers examined their biological effects. They found that the AD-protective SORL1 variants were linked to increased production of the SORL1 protein.
This, in turn, may help clear harmful amyloid-beta from the brain and regulate biological pathways related to immune and nerve cell function. The team also identified a specific SORL1 coding variant that influences how the protein functions—an important discovery that had not been studied in detail before.
Professor Ip emphasized that these findings not only deepen our understanding of Alzheimer’s disease but also open new possibilities for treatment. “Our study shows that SORL1 plays a crucial role in Alzheimer’s disease, and understanding its function could lead to new therapies,” she said.
The research also contributes to one of the most comprehensive East Asian genetic databases for Alzheimer’s, which will be a valuable resource for future studies.
Review and Analysis
This study is a major step forward in Alzheimer’s research, particularly in understanding genetic factors that may protect against the disease. Most previous genetic studies have focused on European populations, but this research highlights the importance of including diverse ethnic groups to get a more complete picture of how Alzheimer’s develops.
One of the key strengths of this study is its large and diverse sample size, which allowed researchers to compare genetic variations across different populations.
The discovery that the Hap_A variant is common in East Asians but rare in Europeans suggests that different populations may have distinct genetic defenses against Alzheimer’s. This insight could help scientists tailor prevention and treatment strategies based on an individual’s genetic background.
Another important finding is that SORL1 protective variants are associated with increased protein expression, suggesting that boosting SORL1 levels could be a potential therapeutic strategy. Future research may explore ways to enhance SORL1function in people who are at risk of Alzheimer’s but do not naturally carry these protective variants.
However, as with any genetic study, this research has some limitations. While it identifies a strong association between certain SORL1 variants and lower Alzheimer’s risk, it does not prove a direct cause-and-effect relationship.
Additional studies, including laboratory experiments and clinical trials, will be needed to confirm whether modifying SORL1 activity can prevent or slow Alzheimer’s progression.
Overall, this study provides valuable new insights into the genetic factors that influence Alzheimer’s risk and protection. It highlights the importance of studying diverse populations and could pave the way for new treatments that target the SORL1 gene to combat Alzheimer’s disease.
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The research findings can be found in Alzheimer’s & Dementia.
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