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US researchers identify, neutralise gene linked to Alzheimer’s

According to the findings of the study published in the journal Nature Medicine, the researchers at Gladstone Institutes in San Francisco focused on a protein associated with the apoE4 gene that damages nerve cells and leads to dementia.

health Updated: Apr 11, 2018 09:11 IST
HT Correspondent
Researchers at a US biomedical institute have modified and neutralised a gene linked with Alzheimer’s disease.
Researchers at a US biomedical institute have modified and neutralised a gene linked with Alzheimer’s disease.(Shutterstock)

Researchers at a US biomedical institute, who are working with human brain cells, have modified and neutralised a gene linked with Alzheimer’s disease.

According to the findings of their study published in the journal Nature Medicine, the researchers at Gladstone Institutes in San Francisco focused on a protein associated with the apoE4 gene that damages nerve cells and leads to dementia.

Having one copy of the apoE4 gene more than doubles a person’s likelihood of developing Alzheimer’s disease, and having two copies of the gene increases the risk by 12-fold, as compared to the most common version of the gene, apoE3, Gladstone Institutes said.

The apoE4 gene creates a protein of the same name, which differs from the apoE3 protein at only one point, but that single change is enough to alter its main structure and function. Scientists have been unclear about why apoE4 is more damaging to brain cells than other versions of the protein.

The researchers were “able to erase the damage caused by apoE4 by changing it, with a small molecule, into a harmless apoE3-like version”.

Lead author Yadong Huang used human cells to model the disease and test new drugs. The researchers created neurons from skin cells donated by Alzheimer’s patients with two copies of the apoE4 gene and from healthy individuals with two copies of the apoE3 gene.

The research confirmed that in human neurons, the misshapen apoE4 protein cannot function properly and is broken down into disease-causing fragments in cells. This process results in several problems commonly found in Alzheimer’s disease.

Once the scientists confirmed apoE4 damages human cells related to Alzheimer’s disease, they looked for ways to repair the abnormalities caused by the gene. Treating human apoE4 neurons with a structure corrector eliminated signs of Alzheimer’s disease, restored normal function to the cells and improved cell survival.

Huang is now working with collaborators in academia and the pharmaceutical industry to improve compounds so they can be tested on human patients.

“Many drugs work beautifully in a mouse model, but so far they’ve all failed in clinical trials. One concern within the field has been how poorly these mouse models really mimic human disease,” Huang said.