Contact: David Weston
University College London
RNA build-up linked to dementia and motor neuron disease
A new toxic entity associated with genetically inherited forms of
dementia and motor neuron disease has been identified by scientists
at the UCL Institute of Neurology. The toxin is the result of a
genetic mutation that leads to the production of RNA molecules
which could be responsible for the diseases. The findings are
published in the journal Acta Neuropathologica.
Frontotemporal dementia and motor neuron disease are related
neurodegenerative diseases that affect approximately 15,000 people
in the UK. Frontotemporal dementia causes profound personality and
behaviour changes. Motor neuron disease leads to muscle weakness
and eventual paralysis.
The most common known cause for both frontotemporal dementia and
motor neuron disease is an unusual genetic mutation in the C9orf72
gene. The mutation involves a small string of DNA letters at the
beginning of the gene, which expand massively to produce thousands
The new research, funded by Alzheimer’s Research UK and the Medical
Research Council, has shown that this DNA expansion acts in a
peculiar way, leading to the generation of unexpected RNA molecules
that could cause the disease.
When a gene is turned on, an RNA copy of the gene’s DNA is
generated. The gene’s DNA code has directionality, so that it is
normally turned on in only one direction, termed the ‘sense
direction’. The new research shows that the DNA expansion is turned
on in both directions.
This leads to the normal sense RNA being produced, as well as RNA
in the opposite direction, termed ‘antisense RNA’. Both RNA types
accumulate into aggregates in the neurons of people with
Intriguingly, the research showed that people with more of these
aggregates in their brains developed the disease earlier than
people with less RNA aggregates. This correlation suggests that the
build-up may be important in causing frontotemporal dementia and
motor neuron disease, making the C9orf72 DNA expansion a potential
target for therapy.
Dr Adrian Isaacs, lead researcher at the UCL Institute of
Neurology, said: “”These findings identify new, potentially toxic
molecules in diseases caused by DNA expansions. The next steps will
be to determine how they might kill neurons and how to stop them
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the
UK’s leading dementia research charity, said: “The discovery of the
C9ORF72 gene was a major step forward for research into
frontotemporal dementia and motor neuron disease, and it’s positive
to see researchers beginning to untangle how this gene may cause
these diseases in some people.
“Alzheimer’s Research UK is delighted to have supported this
promising study. By unravelling some of the biological mechanisms
at play, this research could take us further on the road to new
treatments that are so desperately needed by the thousands of
people with these devastating diseases. For these results to reach
their full potential it’s vital that we continue to invest in
About UCL (University College London)
Founded in 1826, UCL was the first English university established
after Oxford and Cambridge, the first to admit students regardless
of race, class, religion or gender and the first to provide
systematic teaching of law, architecture and medicine.
We are among the world’s top universities, as reflected by our
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second most highly cited European university and the 15th most
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UCL has nearly 25,000 students from 150 countries and more than
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About Alzheimer’s Research UK
Alzheimer’s Research UK is the UK’s leading charity specialising in
finding preventions, treatments and a cure for dementia. To help us
defeat dementia, donate today by visiting
http://www.alzheimersresearchuk.org or calling 0300 111 5555. We
are currently supporting dementia research projects worth over £20
million in leading Universities across the UK.