Alzheimer’s disease is often described by what it leaves behind in the brain, including sticky protein plaques, tangled fibers, and the slow loss of memory and thinking skills. But inherited risk for the disease appears to involve many more genes, cells, and biological pathways than those familiar brain changes alone.
Now, researchers say they have found dozens of new genetic regions tied to Alzheimer’s risk, pointing to parts of the disease that are not the main focus of current treatments.
In the largest common-variant genetic analysis of Alzheimer’s disease to date, researchers analyzed data across multiple datasets from more than 2.8 million people, including 109,479 people with Alzheimer’s, 74,141 proxy cases, and millions of controls. A preprint of the study has been published in medRxiv. It identified 127 genetic regions linked to Alzheimer’s risk, including 48 that had not been reported before.
What Alzheimer’s Genes Can Tell Us
Alzheimer’s disease is the most common cause of dementia, and cases are expected to rise as populations age. Genes play a major role in who develops the disease, but earlier studies had found only part of the risk.
To search for more, the researchers combined data from 30 cohorts across several ancestry groups, including people of European, African, East Asian, admixed American, and South Asian ancestry. Most of the study’s effective sample size still came from people of European ancestry, but the wider approach helped expand the analysis.
Several of the newly identified genes appear connected to immune activity, fat metabolism, the buildup and clearing of amyloid beta, and the ways brain cells interact. Amyloid beta is a protein that can collect into plaques in the brains of people with Alzheimer’s, and many current disease-modifying treatments focus on clearing it, making the other signals especially useful for future research.
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Brain Immune Cells and Neurons Stand Out
One of the clearest signals came from microglia, the brain’s resident immune cells. Microglia help clear debris, respond to injury, and interact with amyloid beta. Previous Alzheimer’s genetic studies have already pointed to these cells, and the new analysis strengthens that connection.
The study also found Alzheimer’s genetic risk signals in several types of neurons, suggesting inherited risk may be tied not only to immune activity in the brain but also to changes in the brain cells that send and receive signals.
Some genes were more active in Alzheimer’s microglia and less active in certain neurons, a pattern that also appeared among genes tied to Alzheimer’s risk. Put simply, inherited risk may influence how the brain responds to damage and how vulnerable some neurons become.
The study also highlighted genes that may matter for future drug research. Among the 48 new genetic regions, researchers found 17 genes that interact with approved drugs.
That does not mean existing drugs are ready to treat Alzheimer’s, but the findings point to possible targets for future research.
Why Genetic Risk Prediction Still Has Limits
The study also improved genetic risk prediction. In one analysis of older European participants in the UK Biobank, people in the top 10 percent of genetic risk had 5.5 times higher Alzheimer’s case prevalence than those in the bottom 10 percent.
Still, the authors note that more than 90 percent of the study’s effective sample size came from people of European ancestry, meaning risk prediction remains less precise for underrepresented groups.
For now, the preprint gives researchers more places to look as they study how Alzheimer’s begins and why some people are more vulnerable than others.
This article is not offering medical advice and should be used for informational purposes only.
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Article Sources
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- This article references information from a preprint published in medRxiv: Genomic analyses reveal new insights into Alzheimer’s disease
