Alzheimer’s Risk Tools Need a Makeover for Diverse Populations

A groundbreaking global study reveals that current genetic tools for predicting Alzheimer’s disease, while effective for some, fall short across diverse ancestries. This highlights the urgent need for more inclusive tools to ensure equitable risk assessment and treatment for all.

The Challenge of Genetic Diversity

A recent investigation, published in Nature Genetics, assessed the applicability of European-derived polygenic risk scores (PGS) for Alzheimer’s disease across various global populations. The research, led by a multi-institutional team, examined whether these scores, developed primarily from European genetic data, could accurately predict Alzheimer’s risk in diverse groups.

The study revealed that while the European-derived scores exhibited significant accuracy in predicting Alzheimer’s onset and biomarker levels in various groups, including Asian, Hispanic, and African ancestries, their effectiveness was diminished in many non-European groups, particularly those of African descent. The integration of data from multiple ancestries, especially when including the key Alzheimer’s risk gene APOE, improved the accuracy of risk prediction for non-European populations.

“Integrating even limited non-European genetic data into current European-derived PGS models can improve predictive accuracy, particularly by better characterizing the effects of the APOE gene region across diverse groups.”

—Dr. Nicolas, Study Author

A 2023 study from the Alzheimer’s Association found that while the overall prevalence of Alzheimer’s is increasing, there are disparities in diagnosis rates, with some racial and ethnic groups experiencing delayed diagnosis, further supporting the need for more equitable tools. (Alzheimer’s Association).

The Study’s Approach

Researchers generated a new PGS, dubbed “PGSALZ,” by utilizing a substantial European GWAS meta-analysis, specifically excluding the UK Biobank to ensure statistical independence. This model focused on 83 Alzheimer’s-associated single-nucleotide polymorphisms (SNPs), excluding the APOE locus.

The novel PGSALZ model was applied to a wide array of populations, including European, East Asian, African, and Hispanic groups, among others. The diverse datasets, obtained from sources like NIAGADS and the Japan’s NBDC, were used to assess the model’s performance. Cross-ancestry models were then compared with the European-only scores to assess performance changes.

Findings and Implications

The European-derived PGSALZ model showed a significant link to Alzheimer’s risk across numerous non-European groups. Yet, some populations, notably those of African ancestry, showed considerably reduced predictive accuracy. The inclusion of the APOE genetic region in the cross-ancestry model enhanced risk prediction for non-European populations.

These findings underscore the necessity of expanding the diversity of GWAS to create equitable, effective genetic tools. As the field advances toward genetic-based interventions, ensuring that risk assessments are useful for everyone, regardless of their ancestry, is crucial for fairness.