MIT Study Reveals How a Rare Alzheimer’s Gene Causes Damage – And a Common Supplement May Help
In the fight against Alzheimer’s disease, scientists are increasingly looking beyond the well-known APOE4 gene. A rare but powerful genetic variant in the ABCA7 gene has emerged as a major risk factor, doubling a person’s chances of developing the disease. Groundbreaking new research from MIT’s Li-Huei Tsai, published in Nature, not only explains how this mutation wreaks havoc on brain cells but also points to a promising countermeasure: a supplement called CDP-choline.
How a Faulty Gene Disrupts the Brain’s “Grease”
The ABCA7 gene produces a protein crucial for managing phospholipids, the fatty molecules that make up cell membranes. The team discovered that loss-of-function (LoF) mutations in this gene create a cascade of problems in neurons:
- Lipid Imbalance: It disrupts the metabolism of a key phospholipid called phosphatidylcholine.
- Stiff Membranes: This leads to an accumulation of “rigid” saturated fats and a decrease in “fluid” unsaturated fats, making neuronal membranes—especially those of mitochondria—too stiff.
- Cellular Power Failure: The stiff mitochondrial membranes can’t function properly, leading to energy deficits and increased oxidative stress.
- Alzheimer’s Pathology: This cellular dysfunction ultimately triggers increased amyloid-beta secretion and neuronal hyperexcitability, hallmarks of Alzheimer’s.
CDP-Choline: A Potential “Universal” Intervention?
The most exciting part of the study was the intervention. The researchers hypothesized that supplementing with CDP-choline—a direct precursor in the phosphatidylcholine synthesis pathway—could restore balance.
They tested this on human neurons engineered to carry the ABCA7 LoF mutation. The results were striking. Supplementation with CDP-choline successfully:
- Restored healthy lipid levels.
- Improved mitochondrial function.
- Reduced oxidative stress.
- Reversed amyloid-related pathology and neuronal hyperexcitability.
This finding is significant because it mirrors the team’s earlier work from 2021, where CDP-choline showed benefits in countering the effects of the APOE4 risk gene. This suggests that despite different genetic starting points, a common pathway of lipid disruption may be a key driver of Alzheimer’s, and CDP-choline could be a broadly beneficial intervention.
CDP-Choline: Benefits, Dosage, and Forms
This research will likely increase interest in CDP-choline. For those curious, it’s important to understand a few key points. The terms CDP-choline vs citicoline are often used interchangeably; citicoline is the common name for the compound sold as a supplement. When considering CDP-choline benefits and side effects, this study points to potential neuroprotective effects, while it is generally considered safe with mild potential side effects like headaches at high doses. As for the optimal CDP-choline dosage, that is still being determined in clinical trials; current supplement studies for cognitive health have used a wide range, but anyone considering it should consult a healthcare provider.
The Bottom Line
This MIT study provides a profound insight: a rare Alzheimer’s gene causes disease by making the brain’s cellular membranes too stiff, leading to a chain reaction of failure. The simple dietary supplement CDP-choline could potentially help reseal these cracks in the brain’s foundation by restoring lipid balance. While more clinical trials are needed, this research opens a promising new avenue for preventing or slowing Alzheimer’s in individuals with high genetic risk.
Source:
von Maydell, D., Wright, S.E., Pao, PC. et al. ABCA7 variants impact phosphatidylcholine and mitochondria in neurons. Nature (2025). https://doi.org/10.1038/s41586-025-09520-y
This article is for informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment.