Having just one copy of the gene, called apoE4, can double your chances of developing Alzheimer’s disease later in life, while having two copies of it can increase your risk a whopping 12-fold.
The team from Gladstone Institutes were able to completely neutralise the gene’s effects by creating a compound that transformed the structure of the apoE4 protein into the completely harmless apoE3 one.
What sets this study apart from so many Alzheimer’s studies however is that the tests were actually carried out on human brain cells, not mice.
Lead author Yadong Huang, MD, PhD and his team were able to use skin cells donated by Alzheimer’s patients and create neurons from them. These neurons then became the testbed for their treatment of the the apoE4 gene.
It’s not entirely clear why apoE4 has such a harmful affect on the brain but what they did see was that the misshapen protein cannot function properly within the human brain and as a result creates the build-up of protein tau and of amyloid peptides that we see in Alzheimer’s patients.
For Huang the real breakthrough was that by testing their methods on human cells they were able to overcome one of the big hurdles that scientists face when trying to treat Alzheimer’s.
“Drug development for Alzheimer’s disease has been largely a disappointment over the past 10 years,” says Huang.
“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 is now working with collaborators in academia and the pharmaceutical industry to improve the compounds so that they can begin full human testing.