New Alzheimer's Risk Genes | Discovery & Drug Potential

A New Strategy for Finding Alzheimer’s Risk

Researchers have identified four previously unknown genes associated with Alzheimer’s disease. This discovery stems from a study published in Science Translational Medicine. The team focused on blood protein signatures rather than standard genetic sequencing. These findings suggest the immune system influences disease progression from outside the brain.

Genetic influence on Alzheimer’s is well-documented but complex. While the ApoE4 gene remains the most significant marker, other variants contribute to risk. Pascal Schlosser of the University of Freiburg led the effort to look beyond traditional genome-wide association studies. His team used a protein-wide approach. This method identifies the functional outcomes of genetic instructions by measuring protein levels in the blood.

Shifting Focus from DNA to Proteins

Standard genome-wide association studies often fail to pinpoint specific mechanisms. Schlosser describes these traditional results as a street address without a house number. You know where to look, but not what is happening. By measuring 1,300 proteins across 9,000 participants, the researchers tracked how genetic differences change protein abundance. This dataset included a diverse group, with roughly one in five participants identifying as African American.

Eighteen proteins linked to Alzheimer’s surfaced during the analysis among European American subjects. Four of the corresponding genes had never appeared in past research. Two of these, LILRB1 and SIRPA, serve as immune system regulators. These proteins function like brakes or checkpoints for immune cells. They dictate whether these cells clear or attack specific targets. The researchers hope this data provides a clearer map for future diagnostic work.

Implications for Future Medical Treatment

Existing cancer treatments already target some of these newly implicated genes. The gene SIRPA and another factor, CD55, respond to current pharmaceutical compounds. This overlap provides a potential path for repurposing drugs. Rather than starting from scratch, scientists might adapt existing medication for Alzheimer’s patients.

Erik Johnson, an assistant professor at Emory University, suggests that bridging the gap between genetic risk and protein changes is vital for drug development. Proteins execute most biological tasks. If researchers can prove these specific proteins influence Alzheimer’s, they gain a target for intervention. Laboratory testing is the next step to confirm these findings. Scientists need to see if altering these proteins actually changes disease risk in a clinical setting.

Addressing the historical lack of diversity in genetic studies remains a priority. While the study found strong signals in European American populations, the results for African American participants were limited. Schlosser acknowledges this reflects a gap in current research samples. Moving toward more inclusive datasets will be necessary to ensure findings apply broadly. The broader scientific community will watch to see if these immune checkpoints can change the trajectory of dementia care.