effectively neutralize it in tests and eliminate signs of the disease in lab-grown neurons.
The gene in question is called apoE4 and has been associated with the
build-up of the tau tangles and beta-amyloid plaques that are linked to
the devastating disease. Previously, studies looking into this
connection and attempting to create drugs to target it have been mired
in problems, mainly as they have tended to focus on mouse models rather
than human cells.
“Drug development for Alzheimer’s disease has been largely a disappointment over the past 10 years,” explained Yadong Huang, who led this latest study published in Nature Medicine.
“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.”
In light of this, the team turned to using human cells in the lab,
and took the skin cells from patients with Alzheimer’s who have two
copies of apoE4 as well as samples from people with the normal variant
known as apoE3, and turned them into stem cells. These were then coaxed
into forming human neurons.
From this, the researchers were able to study exactly how the apoE4
gene variant influences the build-up of the tau proteins and
beta-amyloid plaques that are associated with the development of
Alzheimer’s. After finding that yes, it does indeed cause this build-up
to occur, they then wanted to know how: does the presence of apoE4
causing a loss of apoE3 function, or is it itself causing the toxic
effects seen? These answers are vital as to how we might treat the
“If the damage is caused due to the loss of a protein’s function, you
would want to increase protein levels to supplement those functions,” said Huang.
“But if the accumulation of a protein leads to a toxic function, you
want to lower production of the protein to block its detrimental
The lab-grown human neurons were able to prove that it was indeed the
presence of apoE4 – and not simply the absence of apoE3 – that caused
the damaging proteins to build-up in the cells. This meant that the
researchers could use earlier work they had done in altering the
abnormal apoE4 gene to resemble the innocuous apoE3 gene, using what are
called “structure correctors.”
By targeting the gene in this way, they were in effect able to
neutralize it and restored normal function to the neurons. They now hope
to work with drug companies to see if they are able to translate what
they found into a treatment that can then be put through clinical
Full Article & Source:
Researchers Neutralize A Gene In Human Brain Cells Associated With Alzheimer’s