Common genetic variants matter more in Alzheimer’s than scientists thought
Some researchers had argued that the hunt for common Alzheimer’s risk genes was nearly finished. A new study of 2.8 million people found 48 previously unknown risk regions and nearly tripled estimates of how much common variants contribute.
An extensive international genetic study involving over 2.8 million individuals has uncovered 127 regions of human DNA linked to Alzheimer's disease, including 48 regions previously unknown. The research, published in Nature, reveals that inherited genetic variants contribute to Alzheimer's risk nearly three times more than prior estimates suggested.
This discovery connects genetic vulnerability to elevated gene activity in immune cells of the brain alongside reduced gene activity in nerve cells. The study aimed to discover new Alzheimer's risk loci to understand the causes of the disease and potentially develop new treatments. The team analyzed data from 30 cohorts, totaling more than 2.8 million participants, and identified 127 genetic regions associated with Alzheimer's, with 48 new regions found in the multi-ancestry analysis.
The high-risk ε4 variant of the APOE gene, which transports cholesterol and fats in the brain, showed a modestly stronger association with Alzheimer's in women compared to men. Microglial overactivity and neuronal dampening were observed in brain tissue samples of those with Alzheimer's, indicating that inherited genetic risk is concentrated in microglia and neuronal genes.
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